Base-catalyzed silylation of terminal alkyne c-h bonds

ABSTRACT

The present invention is directed to a mild, efficient, and general direct C(sp)-H bond silylation. Various embodiments includes methods, each method comprising or consisting essentially of contacting at least one organic substrate comprising a terminal alkynyl C—H bond, with a mixture of at least one organosilane and an alkali metal hydroxide, under conditions sufficient to form a silylated terminal alkynyl moiety. The methods are operable in the substantially absence of transition-metal compounds. The systems associated with these methods are also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to U.S. PatentApplication Ser. Nos. 62/044,754, filed Sep. 2, 2014; 62/146,541, filedApr. 13, 2015; and 62/172,969, filed Jun. 9, 2015, the contents of whichare incorporated by reference herein for all purposes.

GOVERNMENT RIGHTS

This invention was made with government support under Grant No.CHE1212767 awarded by the National Science Foundation. The governmenthas certain rights in the invention.

TECHNICAL FIELD

The present invention is directed at methods for silylating alkynesubstrates—i.e., containing terminal alkyne C(sp)-H bonds—using alkalimetal hydroxide, alkoxide, or hydride catalysts and organosilanereagents.

BACKGROUND

The ability to silylate organic moieties has attracted significantattention in recent years, owing to the utility of the silylatedmaterials in their own rights or as intermediates for other importantmaterials used, for example, in agrichemical, pharmaceutical, andelectronic material applications.

Over the past several decades, considerable effort has been allocated tothe development of powerful catalyst architectures to accomplish avariety of C—H functionalization reactions, revolutionizing the logic ofchemical synthesis and consequently streamlining synthetic chemistry.Accomplishing such challenging transformations can often necessitate theuse of stoichiometric additives, demanding reaction conditions, complexligands, and most notably precious metal precatalysts. Notably, the needto use precious metal catalysts for these transformations remains afundamental and longstanding limitation.

Strategies for the synthesis of ethynylsilanes have employed strongbases or have relied on stoichiometric or catalytic transition metalspecies such as Pt, Zn, Au, and Ir, typically using variouspre-activated organosilicon coupling partners at high temperatures.Inexpensive and commercially available hydrosilanes have beeninvestigated, however this particular silicon source has introduced newchallenges: the requisite in situ Si—H bond activation necessitatesexogenous bases, sacrificial hydrogen acceptors or oxidants, andelevated temperatures (i.e., 80-120° C.). Moreover, undesiredhydrosilylation of the alkyne can be competitive, further complicatingcatalyst and reaction design. These factors have led to importantlimitations in scope and practical utility. For example, substrateclasses important in pharmaceuticals and natural products applicationssuch as aliphatic amines and nitrogen heterocycles are notably absent inthe aforementioned reports. Despite the inherent acidity of terminalacetylenes, the development of a mild and general stoichiometric orcatalytic method for cross-dehydrogenative C(sp)-Si bond formationremains a longstanding challenge in the field.

The present invention takes advantage of the discoveries cited herein toavoid at least some of the problems associated with previously knownmethods.

SUMMARY

Herein is disclosed a mild, efficient, and general direct C(sp)-H bondsilylation. The catalytic cross-dehydrogenative method avoids thelimitations of previous strategies and successfully couples alkynes andhydrosilanes previously unprecedented in C—H silylation on multi-gramscale and with high yield and excellent chemoselectivity. Remarkably,the catalysts can be KOH and NaOH.

Various embodiments includes methods, each method comprising orconsisting essentially of contacting at least one organic substratecomprising a terminal alkynyl C—H bond, with a mixture of at least oneorganosilane and an alkali metal hydroxide, alkoxide, or hydride(hydroxide preferred), under conditions sufficient to form a silylatedterminal alkynyl moiety. Such methods are operable in the substantialabsence of transition metal compounds, or other electromagnetic orthermal initiation or propagation.

In some embodiments, the organosilane comprises an organosilane ofFormula (I), Formula (II), or Formula (III):

(R)_(4-m)Si(H)_(m)  (I)

(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)

R—[—SiH(R)—O—]_(n)—R  (III)

where R is flexibly defined, m and p are independently 1, 2, or 3; q is0, 1, 2, 3, 4, 5, or 6; r is 0 or 1; and n is 10 to 100. In someembodiments, for example, the organosilane is independently(R)₃SiH(R)₂SiH₂, or (R)SiH₃. In some embodiments for Formula (II), q is0. In some embodiments for Formula (II), r is 0. In some embodiments, Ris independently alkoxy, alkyl, alkenyl, aryl, aryloxy, heteroaryl,aralkyl, or heteroaralkyl.

In some embodiments, the alkali metal hydroxide is sodium hydroxide(NaOH) or potassium hydroxide (KOH). In some embodiments, the alkalimetal alkoxide is sodium alkoxide (e.g., NaOMe, NaOEt, NaO-t-Bu) orpotassium alkoxide (e.g., KOMe, KOEt, KO-t-Bu, KO-t-amyl). In someembodiments, the alkali metal hydride is sodium hydride (NaH) orpotassium hydride (KH).

The organic substrate is typically defined as having at least oneterminal alkynyl C—H bond having a formula:

R¹—C≡C—H,

where R¹ comprises H, an optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroalkyl, optionallysubstituted heteroaryl, optionally substituted aralkyl, optionallysubstituted heteroaralkyl, or optionally substituted metallocene. Themethods are operable with a wide array of substrates defined in thisway. Compounds having two or more terminal alkyne C—H bonds also providesilylated products, generally in discrete, sequential reactions. Thesubstrates include individual chemical compounds, oligomers, andpolymers.

In certain embodiments employing silanes having two or three Si—H bonds(e.g., R₂SiH₂ or (R)SiH₃), contacting a second or third organicsubstrate comprising a terminal alkynyl C—H bond with the silylatedterminal alkynyl moiety, either at the same time or sequentially, canform a di- or tri-alkynyl silane product.

Once formed, the silylated terminal alkynyl moiety can be subject to avariety of known chemical reactions, and methods employing these knownmethods, when coupled with the inventive methods described here, areconsidered to be within the scope of the present invention. For example,when coupled with the inventive silylating methods described herein, atleast one of the following subsequent reactions are within scope: (a)reacting the silylated terminal alkynyl moiety with another unsaturatedmoiety in a [2+2] or [4+2] cycloaddition reaction to form an aromatic,heteroaromatic, cycloalkenyl, or heterocycloalkenyl moiety; (b) reactingthe silylated terminal alkynyl moiety with a second, unsaturated organicmoiety in a cross-metathesis reaction to form a diolefin or polyolefinproduct; (c) polymerizing the silylated terminal alkynyl moiety; (d)reacting the silylated terminal alkynyl moiety with an organic azide a[3+2] azide-alkyne cycloaddition reaction (generally referred to as“Click chemistry,” including 1,3-dipolar cycloadditions; (e)hydrogenating the silylated terminal alkynyl moiety; (f) removing thesilyl group originally added to the terminal alkynyl C—H bond, such thatthe silylation functions as a blocking group for other transformations;(g) reacting the silylated terminal alkynyl moiety with an aromatichalide compound under conditions sufficient to form an alkynyl-arenelinkage; and (h) reacting the silylated terminal alkynyl moiety with anN-halosuccinimide in the presence of a cationic gold catalyst to producea terminal alkynyl halide.

Additionally, in the case wherein the at least one organosilanecomprises an optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, suchthat the silylated terminal alkynyl moiety comprises a silicon bondedoptionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, certainembodiments include those methods further comprising reacting thesilylated terminal alkynyl moiety with an alcohol and a catalyst underconditions to result in the intramolecular allylation of the silylatedterminal alkynyl moiety

Additionally, in the case wherein the at least one organosilanecomprises a 2-pyridinyl group (as exemplifed herein by(Me)₂(pyridinyl)SiH or (i-Pr)₂(pyridinyl)SiH), the method furthercomprising reacting the silylated terminal alkynyl moiety with a coppercarbomagnesation catalyst and an optionally substituted aryl oroptionally substituted heteroaryl magnesium complex under conditionssufficient to carbomagnesate the silylated terminal alkynyl moiety.Still further embodiments provide reacting the carbomagnesated silylatedterminal alkynyl moiety with an optionally substituted aryl iodide oroptionally substituted heteroaryl iodide in the presence of a palladiumcatalyst to form a trisubstituted silylated olefin. And still furtherembodiments include those where the trisubstituted silylated olefin isreacted with BCl₃ and pinacol under conditions sufficient toborodesilylate the compound, and then optionally reacting theborodesilylated compound with a second optionally substituted aryliodide or optionally substituted heteroaryl iodide under conditionssuitable to cross-couple the resulting C—B bond and the secondoptionally substituted aryl iodide or optionally substituted heteroaryliodide.

Still further embodiments include those systems for silylating anorganic substrate comprising a terminal alkynyl C—H bond, said systemcomprising or consisting essentially of a mixture of (a) at least oneorganosilane and (b) an alkali metal hydroxide, alkoxide, or hydride,and (c) at least one substrate. The systems are described at least interms as sufficient to accommodate the methods described herein. In someembodiments, the system further comprises the presence of a silylatedterminal alkyne derived from the reaction between the substrate and theat least one organosilane.

While the embodiments are described mainly in terms of methods andsystems for affecting these transformations, it should be appreciatedthat any compound derived from these methods and systems, which are nototherwise accessible by other practicable means, are considered withinthe scope of this invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The present application is further understood when read in conjunctionwith the appended drawings. For the purpose of illustrating the subjectmatter, there are shown in the drawings exemplary embodiments of thesubject matter; however, the presently disclosed subject matter is notlimited to the specific methods, devices, and systems disclosed. Inaddition, the drawings are not necessarily drawn to scale. In thedrawings:

FIG. 1 illustrates the range of catalytic C—H silylations now availableby Earth-abundant metal salts. a, Recently disclosed KOt-Bu catalyzedC—H silylation of N-, O-, and S-containing aromatic heterocycles withhigh regiocontrol. b, Alkali metal hydroxides catalyze thecross-dehydrogenative silylation of nonaromatic C(sp)-H bonds.

FIG. 2 illustrates a subset of the optimization reaction conditions andthe scope of utility with respect to the hydrosilane. For Entries 1-6,8, and 10, yields were determined by GC-FID analysis using tridecane asan internal standard. For Entries 7, 9, and 11-20, yields were ofanalytically pure isolated materials. Reactions were conducted on 0.5mmol scale with 0.5 mL of solvent at the prescribed temperature andtime. DME=1,2-dimethoxyethane; DABCO=diazabicyclo[2.2.2]octane;(iPr)₂PySi—H=2-diisopropylsilyl pyridine; Me₂PySi—H=2-dimethylsilylpyridine.

FIG. 3 illustrates the scope of the alkyne substrate. Propargyl alcohol(3x) underwent both O—Si and C—Si dehydrogenative coupling to give thebissilylated product 4x; by contrast, N—Si bond formation was notobserved for N-methyl propargylamine (3w), giving monosilylated 4w. C—Hbonds in bold represent sites that could be engaged by previouslydeveloped C—H functionalization methods, including KOt-Bu catalyzedsilylation, potentially leading to product mixtures. Reactions wereconducted on 0.5 mmol scale with 0.5 mL of solvent at the prescribedtemperature. Yields are of analytically pure isolated materials.Selectivities determined by NMR and GC. DME=1,2-dimethoxyethane.

FIGS. 4A-4E illustrate some of the synthetic applications of theinventive methods. FIG. 4A provides a scheme for the multigram synthesisof unbiased ethynylsilane building block 2a. FIG. 4B shows the step-wisereactivity of symmetrical terminal diynes in both the alkyl- and arylseries can be selectively mono- or bis-functionalized by simplemodification of the reaction conditions. FIG. 4C shows thatdihydrosilanes can undergo double C(sp)-H silylation with NaOH as thecatalyst to furnish diethynylsilanes. These products can be readilyelaborated to polysubstituted siloles. It should be appreciated thatthis, and any of the specific examples provided here should beconsidered exemplars of broader embodiments of the present invention(e.g., in this case, of forming siloles and polysiloles). FIG. 4D showsthat 2-silylpyridine directing groups can be installed onto simplealkynes in good yield. These fragments can be advanced to denselysubstituted olefins. FIG. 4E shows examples of late-stage derivatizationof pharmaceutical substances pargyline and mestranol furnishingsila-therapeutics. In the case of the latter, both O—Si and C—Sidehydrogenative coupling occurs. Reactions were conducted on 0.5 mmolscale with 0.5 mL of solvent unless otherwise stated and at theprescribed temperature. Yields were of analytically pure isolatedmaterials. [Si]=PhMe₂Si; DME=1,2-dimethoxyethane.

FIG. 5 directly compares the reactivities of KOH and NaOH catalystsunder otherwise identical conditions revealing an unanticipated effecton the reaction outcome depending on whether Na⁺ or K⁺ is present.R=PhMe₂Si (10a); R═H (10b). Reaction conditions are equivalent to thosegiven in FIGS. 3 and 4 for each particular hydrosilane and alkyne.Reactions were conducted on 0.5 mmol scale with 0.5 mL of solvent unlessotherwise stated and at the prescribed temperature. Yields are ofanalytically pure isolated materials. DME=1,2-dimethoxyethane.

FIG. 6 directly compares the reactivities of NaOH/KOH and KO-tert-BuOHcatalysts under otherwise identical conditions revealing anunanticipated benefit of using hydroxide vs. alkoxide under certainconditions.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is founded on a set of reactions, each of whichrelies on simple mixtures of organosilanes and strong bases, includingalkali metal hydroxide, alkoxides, and hydrides (preferably hydroxides)which together form in situ systems (the structure and nature of theactive species is still unknown) able to silylate terminal alkynegroups, in the liquid phase, without the presence of transition metalcatalysts, UV radiation or electrical (including plasma) discharges.These reactions are relevant as an important advance in developingpractical methods for the preparation of products important foragrochemical, electronics, fine chemical, and pharmaceuticalapplications. Importantly this reaction is of great interest since itproduces only environmentally benign silicates and dihydrogen as thebyproduct and can avoid toxic metal waste streams as would be observedwith nearly all other approaches proposed in the literature towards thisend. The remarkable facility exhibited by these systems provides auseful tool in the kit of chemists in these fields. This utility can beleveraged when combined with other follow-on reactions.

The present invention may be understood more readily by reference to thefollowing description taken in connection with the accompanying Figuresand Examples, all of which form a part of this disclosure. It is to beunderstood that this invention is not limited to the specific products,methods, conditions or parameters described or shown herein, and thatthe terminology used herein is for the purpose of describing particularembodiments by way of example only and is not intended to be limiting ofany claimed invention. Similarly, unless specifically otherwise stated,any description as to a possible mechanism or mode of action or reasonfor improvement is meant to be illustrative only, and the inventionherein is not to be constrained by the correctness or incorrectness ofany such suggested mechanism or mode of action or reason forimprovement. Throughout this text, it is recognized that thedescriptions refer to compositions and methods of making and using saidcompositions. That is, where the disclosure describes or claims afeature or embodiment associated with a composition or a method ofmaking or using a composition, it is appreciated that such a descriptionor claim is intended to extend these features or embodiment toembodiments in each of these contexts (i.e., compositions, methods ofmaking, and methods of using).

The present invention includes embodiments related chemical systems andmethods for silylating terminal alkynes. Specific embodiments providemethods, each method comprising contacting at least one organicsubstrate comprising a terminal alkynyl C—H bond, with a mixture of atleast one organosilane and an alkali metal hydroxide, alkoxides, andhydrides (preferably hydroxides), under conditions sufficient to form asilylated terminal alkynyl moiety. The reaction operate well in thecomplete absence of (or substantially complete absence) oftransition-metal compounds. Likewise, these methods are also operable inthe absence or substantially complete absence of other electromagneticor thermal triggers needed for initiation or propagation. That is, theseembodiments do not need UV irradiation or electric or plasma dischargeconditions to operate.

As used herein to describe the systems and methods, the terms“organosilane” or “hydrosilane” may be used interchangeably and refer toa compound or reagent having at least one silicon-hydrogen (Si—H) bondand one carbon-containing moiety. The organosilane may further contain asilicon-carbon, a silicon-oxygen (i.e., encompassing the term“organosiloxane”), a silicon-nitrogen bond, or a combination thereof,and may be monomeric, or contained within an oligomeric or polymericframework, including being tethered to a heterogeneous or homogeneoussupport structure. In certain embodiments, these organosilane maycomprise at least one compound of Formula (I), Formula (II), or Formula(III):

(R)_(4-m)Si(H)_(m)  (I)

(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)

R—[—SiH(R)—O—]_(n)—R  (III)

where: m and p are are independently 1, 2, or 3; q is 0, 1, 2, 3, 4, 5,or 6; r is 0 or 1; n is 10 to 100; and each R is independently halo(e.g., F, Br, Cl, I)(provided at least one R is contains carbon),optionally substituted C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted C₁₋₁₂ alkenyl or heteroalkenyl, optionally substituted C₁₋₁₂alkynyl or heteroalkynyl, optionally substituted C₅₋₂₀ aryl or C₃₋₂₀heteroaryl, optionally substituted C₆₋₃₀ alkaryl or heteroalkaryl,optionally substituted C₅₋₃₀ aralkyl or heteroaralkyl, optionallysubstituted —O—C₁₋₁₂ alkyl or heteroalkyl, optionally substituted—O—C₅₋₂₀ aryl or —O—C₃₋₂₀ heteroaryl, optionally substituted —O—C₅₋₃₀alkaryl or heteroalkaryl, or optionally substituted —O—C₅₋₃₀ aralkyl orheteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato, isocyanate,thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl,siloxazanyl, boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.Exemplary, non-limiting organosilanes may independently include (R)₃SiHor (R)₂SiH₂, or (R)SiH₃. In some embodiments for Formula (II), q is 0.In some embodiments for Formula (II), r is 0. In some embodiment R isindependently alkoxy, alkyl, alkenyl, aryl, aryloxy, heteroaryl,aralkyl, or heteroaralkyl. In certain embodiments, (R)₃SiH include theuse of alkyl, aryl, heteraryl, alkoxy, or mixed alkyl-aryl silanes oralkyl-heteroaryl silanes, for example, EtMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂,PhMe₂SiH, BnMe₂SiH, (EtO)₃SiH, (i-Pr)₃SiH, Me₂(pyridinyl)SiH, or(i-Pr)₂(pyridinyl)SiH, or Me₃Si—SiMe₂H. Embodiments involvingR₂(pyridinyl)SiH silanes (i.e., the methods and systems involving them)are particularly unique as the inventors are unaware of these havingever been incorporated by a catalytic system of any type. Polymericmaterials, such as polymethylhydrosiloxane (PMHS), are also effective.

The use of organosilanes of general structure (R)₂SiH₂ and (R)SiH₃ alsowork well, and provide for opportunities for coupling or bridgingreactions, as described herein. In the presence of a single substrate,bis-alkynyl silanes have been be isolated in good yield (see, e.g.,Example 3.4; FIG. 4C). It is possible that at sufficiently mildconditions, the corresponding mono-alkynyl silane may be accessible, butthat has yet to be observed. Interestingly, the R₂SiH₂ (and (R)SiH₃)organosilanes may also be reacted with different substrates to yieldsymmetric and asymetric bis- or tri-alkynyl silanes (again, see, e.g.,Example 3.4). Note that Example 3.4 describes a reaction of equimolaramounts of two different substrates, resulting in a product mix that waspredominantly (76%) cross-coupled. The reason for this substantialenrichment of the cross-coupled product, relative to what might havebeen expected from a purely statistical combination of the twosubstrates, is unknown, but suggests that this inventive methodology mayprovide a useful tool for the preferential formation of such di- or trialkynyl cross-coupled silane products.

Additionally, the use of aceylene or poly-yne substrates, in thepresence of R₂SiH₂ or silanes of Formula (II) may be useful forpreparing polymeric or cyclic ethynlsilanes, non-limiting examples ofwhich include the structure units:

Some of these structures have been described by Gleiter, R. and D. B.Werz, Chem. Rev. 2010, 110, 4447-4488, which is incorporated byreference herein in its entirety for all purposes.

Previously, some of the inventors reported the use of potassium alkoxideand hydroxide catalysts to effect the silylation of aromatic andheteroaromatic substrates, and noted that potassium-based bases wereunique in their ability in this regard. Here, the inventors haveidentified that, while potassium (and sodium) alkoxides (and in somecases KH) can be used with some substrates, the scope of the reaction isrelatively limited (see, e.g., FIG. 6). In silylating terminal alkyneC—H groups, the use of alkali metal hydroxides, especially sodiumhydroxide (NaOH) and potassium hydroxide (KOH) offers the possibility tosilylate a much wider and more varied array of substrates.Interestingly, and for reasons not entirely understood, certainorganosilane-substrate combinations practically operate to good yieldwith either KOH or NaOH (e.g., EtMe₂SiH, PhMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂,(i-Pr)₂(pyridinyl)SiH, or Me₂(pyridinyl)SiH), while others appear torespond better to the use of NaOH(PhMe₂SiH, BnMe₂SiH, (EtO)₃SiH,Me₂(pyridinyl)SiH, or Me₃Si—SiMe₂H), and still others respond better tothe use of KOH ((i-Pr)₃SiH, or (i-Pr)₂(pyridinyl)SiH), at least underthe mild reaction conditions described herein (see, e.g., FIG. 5). Thiscation effect (NaOH vs. KOH) also appears to depend on the natures ofthe substrate (compare reactivity of Me₂PhSiH with various substrates inFIG. 5). The mechanistic reason for this unique and previouslyunrecognized cation effect is not yet understood. The ability of NaOHand sodium alkoxides (Table 1) to affect these silylations is especiallyinteresting, given their unworkability in other aryl and heteroarylsystems. Note that the reference to independent use of sodium hydroxide,sodium alkoxide, potassium hydroxide, and potassium alkoxides, whilepreferred do not preclude these materials being used in any combinationwith one another, and these mixtures are seen as additional embodiments.

The Examples provide exemplary reaction conditions useful for effectingthe desired transformations. In other embodiments, substrates, alkalimetal hydroxides, alkoxides, and hydrides (preferably hydroxides), andorganosilanes may be heated to temperatures ranging from 0° C. to 150°C., or higher, for times ranging from 24 hours to several days, thoughpractically, the reactions proceed to good yield and selectivity whenconducted at a temperate in a range of ambient room temperature (e.g.,25° C.) to about 85° C. Interesting, it is shown within this applicationthat by staging the reaction temperatures (for example, from even 45° C.to 65° C.), it is possible to select and provide products that areeither monosilylated or disilylated on substrates having two apparentlyequivalent terminal alkynyl C—H bonds (see, e.g., Example 3.3, FIG. 4B).

These methods typically employ hydrocarbon or ether-based solvents, orcan be operated without solvent. Ether solvents, such astetrahydrofurans (including 2-methyltetrahydrofuran), diethyl anddimethyl ether, 1,2-dimethoxyethane, dioxane, and alkyl terminatedglycols have been shown to work well.

The methods are fairly flexible with respect to substrates, particularlywhen considering NaOH, KOH, or mixtures thereof. The inventive methodsprovide for the silylation of a wide range of substrates having one,two, or more terminal alkynyl C—H bonds with remarkable efficiency. Insome embodiments, the organic substrate comprising the terminal alkynylC—H bond is described in term of a formula:

R¹—C≡C—H,

where R¹ comprises H, an optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroalkyl, optionallysubstituted heteroaryl, optionally substituted aralkyl, optionallysubstituted heteroaralkyl, or optionally substituted metallocene. R¹ mayinclude individual molecular moieties or be oligomeric or polymeric.

Independent embodiments include those where R¹ is or comprises:

-   -   (a) an optionally substituted linear alkyl, an optionally        substituted branched alkyl, or an optionally substituted        cycloalkyl;    -   (b) an optionally substituted linear alkenyl, an optionally        substituted branched alkenyl, or an optionally substituted        cycloalkenyl;    -   (c) an optionally substituted linear heteroalkyl, an optionally        substituted branched heteroalkyl, or an optionally substituted        heterocycloalkyl;    -   (d) an optionally substituted aryl, an optionally substituted        aralkyl, optionally substituted heteroaryl, or an optionally        substituted heteroaralkyl; or    -   (e) a combination of any two or more types of substituents        listed in (a) through (d).

In more specific embodiments, R¹ is or comprises:

-   -   (a) an optionally substituted benzene, biphenyl, naphthalene, or        anthracene ring structure; or    -   (b) an optionally substituted furan, pyrrole, thiophene,        pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole,        isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine,        pyrazine, triazone, benzofuran, benzopyrrole, benzothiophene,        isobenzofuran, isobenzopyrrole, isobenzothiophene, indole,        isoindole, indolizine, indazole, azaindole, benzisoxazole,        benzoxazole, quinoline, isoquinoline, cinnoline, quinazoline,        naphthyridine, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,        2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol,        or dibenzothiophene moiety; or    -   (c) the organic substrate comprising the terminal alkynyl C—H        bond is polymeric.

Each of the substrates and organosilanes represent specific examples andembodiments of the materials within the scope of the present invention.

Once formed, the silylated terminal alkynyl moiety can be subject to avariety of known chemical reactions, and the present inventioncontemplates that methods employing these known methods, when coupledwith the inventive methods described here, are within the scope of thepresent invention. For the sake of clarity, the term “original silylatedproduct” is introduced here to represent the silylated product of theinventive methods, this original silylated product containing thesilylated terminal alkynyl moiety previously described. Except asotherwise specified, the reactions which follow represent excellent waysin which to incorporate silyl groups in the final products.

For example, alkynes are useful synthons in forming silylated aromatic,heteroaromatic, cycloalkenyl, or heterocycloalkenyl moieties usingDiels-Alder type [2+2] or [4+2] cycloaddition reaction. Thepre-incorporation of silyl groups attached to the alkyne group of thepresent products provides an interesting alternative means toincorporate silyl groups on such aromatic, heteroaromatic, cycloalkenyl,or heterocycloalkenyl products. Accordingly, in some embodiments of thepresent invention, the silylated terminal alkynyl moiety formed by thepresent methods may be further reacted with another unsaturated moiety(for example an optionally substituted alkene, alkyne, azide, nitrile,isocynate, isothiocyanate, carbonyl, amide, urea, etc.) to form asilylated aromatic, heteroaromatic, cycloalkenyl, or heterocycloalkenylstructure. This “another unsaturated moiety” may be introduced as aseparate molecular entity (i.e., an intermolecular reaction) or may bepresent in the original silylated product (i.e., an intramolecularreaction)—see e.g., FIG. 4C for but one example of this. In either case,the original silylated product may or may not need to be isolated beforeeffecting the cyclization, and if the latter, the reaction may beconducted in a single pot synthesis.

In other embodiments, the original silylated product may also be reactedwith a second, unsaturated organic moiety (cyclic or acyclic, comprisingoptionally substituted alkene, alkyne, azide, nitrile, isocynate,isothiocyanate, carbonyl, amide, urea, etc.) in a cross-metathesisreaction to form a silylated diolefin or polyolefin product. Suchcross-metathesis metathesis reactions are well-known, and the person ofordinary skill would know how to effect these transformations. Forexample, the use of Grubbs-type ruthenium carbene metathesis catalystsmay be used for this purpose, though the contemplated transformationsare not limited to these types of catalysts. These may be representedschematically as:

Again, the reactions may be intra- or intermolecular, single- ormulti-pot syntheses, and provide another method for incorporating silylgroups under facile and mild conditions. Such downstream transformationsare described, for example, in Kim, et al., J. Amer. Chem. Soc., 126(33), 2004, 10242-10243, which is incorporated by reference herein forits teaching in at least this regard. These products may then be subjectto the Diels-Alder type [2+2] or [4+2] cycloaddition reactions describedabove.

Alternatively, or additionally, the original silylated product may becopolymerized with an optionally substituted enyne, diene, diyne, orcyclic olefin, using any suitable catalyst(s) to form silylatedpolymers. In certain embodiments, these reactions may comprisemetathesis polymerization, for example ROMP. Such metathesispolymerization reactions are well-known, and the person of ordinaryskill would know how to affect them, for example, again usingGrubbs-type ruthenium carbene metathesis catalysts, though thecontemplated transformations are not limited to these types ofcatalysts. Again, the reactions may be intra- or intermolecular, single-or multi-pot syntheses, and provide another method for incorporatingsilyl groups into polymers under facile and mild conditions. Forexample, such methods may provide silylated conducting polyacetylenepolymers that would be useful in electronic applications.

In other embodiments, the original silylated product may be furtherreacted to hydrogenate the silylated terminal alkynyl moiety. Thissilylated terminal alkynyl moiety may also be reacted with water,alcohols, hydrogen cyanide, hydrogen chloride, dihalogen, or carboxylicacids under conditions known to give corresponding vinyl compounds orcarbonyl-type compounds. Again, the skilled artisan would be able toaffect these transformations without undue effort.

In other embodiments, the original silylated product may be reacted withn organic azide in a [3+2]azide-alkyne cycloaddition reaction, forexample forming silylated triazoles. Such reactions are also well-known,as so-called Click chemistry, which include 1,3-dipolar cycloadditions.Such reactions may be inter- or intramolecular reaction and aretypically catalyzed by copper, copper-iron, or ruthenium-containingcatalysts. Again, it would be well within the skills of a person ofordinary skill to affect such transformations without undue burden.

Other embodiments provide that alkynyl aryl silanes react with, forexample, triflic acid, to form silanols. See, for example, Franz, A. K.,et al., J. Med. Chem., 2013, 56, 388-405, which is incorporated byreference herein in its entirety for all purposes. Accordingly, certainembodiments of this invention provide for the further reaction of theoriginal silylated product with triflic acid to form the correspondingsilanol. As the present invention also allows for the incorporation ofalkoxy silanes (e.g., (RO)₃SiH), similar silanol products can beprepared simply by hydrolyzing the original silylated product, wherethat original silylated product contains comprises an alkoxysilyl group.

The mildness of the conditions in these inventive methods, and theabsence of any need for transition metal catalysts, makes themespecially suitable for pharmaceutical or medicinal applications, silylderivatives have been shown to be particularly important. In addition tothe use of the inventive silyl derivatives for mechanisticdeterminations of modes of action, of enhancing tissue penetration,altering hydrogen-bonding effects, and lack of known toxicity effects,organosilicon compounds are finding use as biological imaging agents.The inventive silylated terminal alkynes can be expected to be effectivein their own right for these purposes, as the methods allow for theincorporation of a wide variety of silyl moieties at virtually any stagein a drug's synthesis. Additionally, siloxylated terminal olefins (e.g.,where the silylated terminal alkynyl moiety comprises an —Si(OR)₃ group)may further be reacted with, for example KHF₂, to formtetrafluorosilicate groups—i.e, as R¹—C≡C—SiF₄ ⁻ compounds (orradiolabeled ¹⁸F versions thereof). Such transformations and advantagesare described, for example, in Franz, A. K., et al., J. Med. Chem.,2013, 56, 388-405.

The inventive terminal alkynyl silanes may also be activated by fluorideor alkoxides, with the associated removal of the silyl group to formalkynyl nucleophiles which can then react with electrophiles.Accordingly, other embodiments also provide for the reaction of thesilylated terminal alkynyl moiety with a fluoride containing salt (e.g.,alkali metal or tetra-aryl, tetra-alkyl, or mixed alkyl/aryl ammoniumsalts) with or without the presence of an acid stronger then HF togenerate an activated, desilylated alkynyl nucleophile, to be added toother substrates, for example, alkyl halides (or any alkyl group with asuitable leaving group, including without limitation tosylates,triflates, or any alcohol, amine, or carboxylic acid protecting group),acyl halides (including acyl chlorides), substituted alkene (e.g.,Michael addition acceptors), enones (or generally α,β-unsaturatedcarbonyl compounds), epoxides, esters, α-keto-esters (includingtrifluoro- or other substituted pyruvate), etc. In the presence ofchiral palladium catalysts, such as (but not limited to) (S)-BINAP-Pd²⁺catalysts, the reaction may be done to yield optically active additionproducts. Such chemistry is described, for example, in Aikawa, K., etal., Org. Lett., 12, 5716-5719 (2010), which is incorporated byreference for all purposes.

In other embodiments, the original silylated product may be furtherreacted simply to remove the silyl group originally added to theterminal alkynyl C—H bond and replace it with a hydrogen, deuterium, ortritium atom. This could be accoomplished, for example, simply byquenching the desilylated alkynyl nucleophile with a protic (ofisotopic) source. Such a strategy would be useful if the silyl group wasoriginally added to protect the otherwise acidic terminal alkynyl C—Hgroup from reactions conducted on the substrate away from this C—Hgroup, or act as a directing group (e.g., see the carbomagnesationreactions described below). In still other embodiments, the silylatedterminal alkynyl moiety may be reacted with an N-halosuccinimide in thepresence of a cationic gold catalyst to produce a terminal alkynylhalide, where halo is preferably bromo or iodo. Again, such reactionsare known and described, for example, in Starkov, et al., Adv. Synth.Catal., 2012, 354, pp. 3217-3224, which is incorporated by referenceherein in its entirety for all purposes.

In other embodiments, the original silylated product may be furtherreacted with an aromatic halide compound under conditions sufficient toform an alkynyl-arene linkage, for example using Pd/Cu catalysts, suchas Pd(PPh₃)₂Cl₂, CuI catalysts and optionally substituted iodo or bromoaromatic compounds. E.g.,

where R and R¹ are as described above, and [Het]Ar—X refers to anoptionally substituted aryl or heteroaryl bromide or iodide.

In other specific embodiments, wherein the at least one organosilanecomprises an optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, suchthat the silylated terminal alkynyl moiety comprises a silicon bondedoptionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, the silylatedterminal alkynyl moiety may further be reacted with an alcohol and acatalyst under conditions to result in the intramolecular allylation ofthe silylated terminal alkynyl moiety:

where R and R¹ are as described above. Such reactions have beendescribed, for example, in Park and Lee, J. Amer. Chem. Soc. 2006, 128,10664-10665, which is incorporated by reference herein in its entiretyfor all purposes.

In the specific case wherein the at least one organosilane comprises a2-pyridinyl group (of which (Me)₂(pyridinyl)SiH or (i-Pr)₂(pyridinyl)SiHare but two non-limiting examples), further embodiments provide methodsin which the silylated terminal alkynyl moiety is reacted with a coppercarbomagnesation catalyst and an optionally substituted aryl oroptionally substituted heteroaryl magnesium complex under conditionssuitable and sufficient sufficient to carbomagnesate the silylatedterminal alkynyl moiety. Such reactions are well-documented, for examplein Itami, et al., Synlett 2006, No. 2, 157-180, which is incorporated byreference herein in its entirety for all purposes. In such cases, forexample, the reaction of an original silylated product as shown below,with an optionally substituted aromatic magnesium complex, such asdescribed in terms of [Het]Ar¹—MgI, results in a correspondingcarbomagnesated product:

where R and R¹ are as described above, and [Het]Ar¹ is an optionallysubstituted aryl or heteroaryl moiety, again as described above. Theconditions useful for carrying out this and the followingtransformations are available in the Itami reference cited above.Thecombined reactions are a powerful way of forming stereospecificproducts.

The carbomagnesated silylated terminal alkynyl moiety may then bereacted with an optionally substituted aryl iodide or optionallysubstituted heteroaryl iodide (designated here as [Het]Ar²) in thepresence of a palladium catalyst to form a trisubstituted silylatedolefin. For example,

where [Het]Ar² is also an optionally substituted aryl or heteroarylmoiety, again as described above, which may be the same or differentthan [Het]Ar¹.

The trisubstituted silylated olefin may then reacted with BCl₃ andpinacol under conditions sufficient to borodesilylate the compound. Inseparate steps, the borodesilylated compound may be reacted with asecond optionally substituted aryl iodide or optionally substitutedheteroaryl iodide under conditions suitable to cross-couple theresulting C—B bond and the second optionally substituted aryl iodide oroptionally substituted heteroaryl iodide. These reactions are shownschematically as:

where [Het]Ar³ is also an optionally substituted aryl or heteroarylmoiety, again as described above, which may be the same or differentthan [Het]Ar¹ or [Het]Ar². The borodesilylation reactions have beenpreviously described, for example, in Babudri, et al., Tetrahedron 1998,54, 1085) as have the Suzuki-Miyaura-type boron-based crosscouplingreactions (e.g., see (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95,2457; and (b) Miyaura, N. Top. Curr. Chem. 2002, 219, 11). Each of thesereferences is incorporated by reference herein in their entireties forall purposes.

It should be appreciated that hydrogenating the original silylatedproduct containing a a 2-pyridinyl silyl group can result in thecorresponding 2-pyridinyl silyl olefin, and that the reference to Itami(i.e., Itami, et al., Synlett 2006, No. 2, 157-180) describes a richchemistry of such compounds. To the extent allowable by local law, suchtransformations of products derived from the inventive methods describedin the present disclosure are also considered within the scope of thepresent invention.

The inventive concepts have been thusfar described in terms of themethods of catalytically silylating terminal alkynyl C(sp)-H bonds. Itshould be appreciated that the products obtained from such methods, tothe extent that they are not practically available by other means knownat the time of this filing, and the systems used in these methods, areall considered within the scope of the present disclosure.

Again, the present invention includes embodiments for any systemnecessary to affect any of the methods described herein. For example,certain embodiments provide systems for silylating an organic substratecomprising a terminal alkynyl C—H bond, each system comprising orconsisting essentially of a mixture of (a) at least one organosilane and(b) an alkali metal hydroxide (and in some cases, sodium or potassiumalkoxide or hydride, or a mixture thereof), and (c) at least onesubstrate. Such systems typically include the substrate(s) upon whichthe system is operable, the substrates comprising at least one terminalalkynyl C(sp)-H moiety. Typically, the system is substantially free oftransition-metal compounds, or where present, the transition metal maybe considered a spectator to the reaction. In some embodiments, thesystem further comprises the presence of a silylated terminal alkynederived from the reaction between the substrate and the at least oneorganosilane.

In such systems, the at last one organosilane comprises an organosilaneof Formula (I), Formula (II), or Formula (III):

(R)_(4-m)Si(H)_(m)  (I)

(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)

R—[—SiH(R)—O—]_(n)—R  (III)

where: m, n, p, q, r and R are described elsewhere. Similarly, invarious independent embodiments of the systems:

-   -   (a) the organosilane is (R)₃SiH, (R)₂SiH₂, or (R)SiH₃;    -   (b) R independently comprises alkoxy, alkyl, alkenyl, aryl,        aryloxy, heteroaryl, aralkyl, or heteroaralkyl;    -   (c) the alkali metal hydroxide is sodium hydroxide (NaOH),        potassium hydroxide (KOH), or a combination thereof;    -   (d) the alkali metal alkoxide is a sodium hydroxide, potassium        alkoxide (KOH), or a combination thereof;    -   (e) the organic substrate comprising the terminal alkynyl C—H        bond has a formula:

R¹—C≡C—H,

where R¹ is defined according to any of the method embodiments describedabove.

TERMS

In the present disclosure the singular forms “a,” “an,” and “the”include the plural reference, and reference to a particular numericalvalue includes at least that particular value, unless the contextclearly indicates otherwise. Thus, for example, a reference to “amaterial” is a reference to at least one of such materials andequivalents thereof known to those skilled in the art, and so forth.

When a value is expressed as an approximation by use of the descriptor“about,” it will be understood that the particular value forms anotherembodiment. In general, use of the term “about” indicates approximationsthat can vary depending on the desired properties sought to be obtainedby the disclosed subject matter and is to be interpreted in the specificcontext in which it is used, based on its function. The person skilledin the art will be able to interpret this as a matter of routine. Insome cases, the number of significant figures used for a particularvalue may be one non-limiting method of determining the extent of theword “about.” In other cases, the gradations used in a series of valuesmay be used to determine the intended range available to the term“about” for each value. Where present, all ranges are inclusive andcombinable. That is, references to values stated in ranges include everyvalue within that range.

It is to be appreciated that certain features of the invention whichare, for clarity, described herein in the context of separateembodiments, may also be provided in combination in a single embodiment.That is, unless obviously incompatible or specifically excluded, eachindividual embodiment is deemed to be combinable with any otherembodiment(s) and such a combination is considered to be anotherembodiment. Conversely, various features of the invention that are, forbrevity, described in the context of a single embodiment, may also beprovided separately or in any sub-combination. Finally, while anembodiment may be described as part of a series of steps or part of amore general structure, each said step may also be considered anindependent embodiment in itself, combinable with others.

The transitional terms “comprising,” “consisting essentially of,” and“consisting” are intended to connote their generally in acceptedmeanings in the patent vernacular; that is, (i) “comprising,” which issynonymous with “including,” “containing,” or “characterized by,” isinclusive or open-ended and does not exclude additional, unrecitedelements or method steps; (ii) “consisting of” excludes any element,step, or ingredient not specified in the claim; and (iii) “consistingessentially of” limits the scope of a claim to the specified materialsor steps “and those that do not materially affect the basic and novelcharacteristic(s)” of the claimed invention. Embodiments described interms of the phrase “comprising” (or its equivalents), also provide, asembodiments, those which are independently described in terms of“consisting of” and “consisting essentially of.” For those embodimentsprovided in terms of “consisting essentially of,” the basic and novelcharacteristic(s) is the facile operability of the methods to providesilylated products at meaningful yields (or the ability of the systemsused in such methods to provide the product compositions at meaningfulyields or the compositions derived therefrom) to silylate terminalalkynyl C(sp)-H moieties using only those ingredients listed. In thoseembodiments that provide a system or method comprises the use of amixture consisting essentially of the substrate, organosilane(alternatively referred to as hydrosilane), and strong base (sodium orpotassium hydroxide, alkoxide, or hydride), it refers to the fact thatthis system operates to silylate the substrate at rates corresponding tothose described herein under comparable conditions as described hereinwithout additional (e.g., transition metal) catalysts or plasma or UVradiation sources. While some level of transition metals may be present(for example, as a substrate), they are not needed for the operabilityof the methods, and may be considered spectators for purposes of thisreaction. Indeed, extensive experiments and analyses conducted rule outcatalysis by adventitious transition metal residues (see Example 2.1.2,Table 2). Similarly, while other previous silylation reactions haveemployed plasma or UV irradiation to operate, the present invention doesnot require these energy sources. The additional presence of theseenergy sources should not be seen as replacing the basis underlyingoperability of the present methods. The term “meaningful product yields”is intended to reflect product yields of greater than 50%, but whenspecified, this term may also refer to yields of 10%, 20%, 30%, 40%,50%, 60%, 70%, 80%, or 90% or more, relative to the amount of originalsubstrate.

When a list is presented, unless stated otherwise, it is to beunderstood that each individual element of that list, and everycombination of that list, is a separate embodiment. For example, a listof embodiments presented as “A, B, or C” is to be interpreted asincluding the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,”or “A, B, or C.” Similarly, a designation such as C₁₋₃ includes C₁, C₂,C₃, C₁₋₂, C₂₋₃, C_(1,3), as separate embodiments, as well as C₁₋₃.

Throughout this specification, words are to be afforded their normalmeaning, as would be understood by those skilled in the relevant art.However, so as to avoid misunderstanding, the meanings of certain termswill be specifically defined or clarified.

The term “alkyl” as used herein refers to a linear, branched, or cyclicsaturated hydrocarbon group typically although not necessarilycontaining 1 to about 24 carbon atoms, preferably 1 to about 12 carbonatoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,tert-butyl, octyl, decyl, and the like, as well as cycloalkyl groupssuch as cyclopentyl, cyclohexyl and the like. Generally, although againnot necessarily, alkyl groups herein contain 1 to about 12 carbon atoms.The term “lower alkyl” intends an alkyl group of 1 to 6 carbon atoms,and the specific term “cycloalkyl” intends a cyclic alkyl group,typically having 4 to 8, preferably 5 to 7, carbon atoms. The term“substituted alkyl” refers to alkyl groups substituted with one or moresubstituent groups, and the terms “heteroatom-containing alkyl” and“heteroalkyl” refer to alkyl groups in which at least one carbon atom isreplaced with a heteroatom. If not otherwise indicated, the terms“alkyl” and “lower alkyl” include linear, branched, cyclic,unsubstituted, substituted, and/or heteroatom-containing alkyl and loweralkyl groups, respectively.

The term “alkylene” as used herein refers to a difunctional linear,branched, or cyclic alkyl group, where “alkyl” is as defined above.

The term “alkenyl” as used herein refers to a linear, branched, orcyclic hydrocarbon group of 2 to about 24 carbon atoms containing atleast one double bond, such as ethenyl, n-propenyl, isopropenyl,n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl,eicosenyl, tetracosenyl, and the like. Preferred alkenyl groups hereincontain 2 to about 12 carbon atoms. The term “lower alkenyl” intends analkenyl group of 2 to 6 carbon atoms, and the specific term“cycloalkenyl” intends a cyclic alkenyl group, preferably having 5 to 8carbon atoms. The term “substituted alkenyl” refers to alkenyl groupssubstituted with one or more substituent groups, and the terms“heteroatom-containing alkenyl” and “heteroalkenyl” refer to alkenylgroups in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkenyl” and “lower alkenyl”include linear, branched, cyclic, unsubstituted, substituted, and/orheteroatom-containing alkenyl and lower alkenyl groups, respectively.

The term “alkenylene” as used herein refers to a difunctional linear,branched, or cyclic alkenyl group, where “alkenyl” is as defined above.

The term “alkynyl” as used herein refers to a linear or branchedhydrocarbon group of 2 to about 24 carbon atoms containing at least onetriple bond, such as ethynyl, n-propynyl, and the like. Preferredalkynyl groups herein contain 2 to about 12 carbon atoms. The term“lower alkynyl” intends an alkynyl group of 2 to 6 carbon atoms. Theterm “substituted alkynyl” refers to an alkynyl group substituted withone or more substituent groups, and the terms “heteroatom-containingalkynyl” and “heteroalkynyl” refer to alkynyl in which at least onecarbon atom is replaced with a heteroatom. If not otherwise indicated,the terms “alkynyl” and “lower alkynyl” include a linear, branched,unsubstituted, substituted, and/or heteroatom-containing alkynyl andlower alkynyl group, respectively.

The term “alkoxy” as used herein intends an alkyl group bound through asingle, terminal ether linkage; that is, an “alkoxy” group may berepresented as —O-alkyl where alkyl is as defined above. A “loweralkoxy” group intends an alkoxy group containing 1 to 6 carbon atoms.Analogously, “alkenyloxy” and “lower alkenyloxy” respectively refer toan alkenyl and lower alkenyl group bound through a single, terminalether linkage, and “alkynyloxy” and “lower alkynyloxy” respectivelyrefer to an alkynyl and lower alkynyl group bound through a single,terminal ether linkage.

The term “aromatic” refers to the ring moieties which satisfy the Hückel4n+2 rule for aromaticity, and includes both aryl (i.e., carbocyclic)and heteroaryl (also called heteroaromatic) structures, including aryl,aralkyl, alkaryl, heteroaryl, heteroaralkyl, or alk-heteroaryl moieties,or pre-polymeric (e.g., monomeric, dimeric), oligomeric or polymericanalogs thereof.

The term “aryl” as used herein, and unless otherwise specified, refersto an aromatic substituent or structure containing a single aromaticring or multiple aromatic rings that are fused together, directlylinked, or indirectly linked (such that the different aromatic rings arebound to a common group such as a methylene or ethylene moiety). Unlessotherwise modified, the term “aryl” refers to carbocyclic structures.Preferred aryl groups contain 5 to 24 carbon atoms, and particularlypreferred aryl groups contain 5 to 14 carbon atoms. Exemplary arylgroups contain one aromatic ring or two fused or linked aromatic rings,e.g., phenyl, naphthyl, biphenyl, diphenylether, diphenylamine,benzophenone, and the like. “Substituted aryl” refers to an aryl moietysubstituted with one or more substituent groups, and the terms“heteroatom-containing aryl” and “heteroaryl” refer to aryl substituentsin which at least one carbon atom is replaced with a heteroatom, as willbe described in further detail infra.

The term “aryloxy” as used herein refers to an aryl group bound througha single, terminal ether linkage, wherein “aryl” is as defined above. An“aryloxy” group may be represented as —O-aryl where aryl is as definedabove. Preferred aryloxy groups contain 5 to 24 carbon atoms, andparticularly preferred aryloxy groups contain 5 to 14 carbon atoms.Examples of aryloxy groups include, without limitation, phenoxy,o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy,m-methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy,3,4,5-trimethoxy-phenoxy, and the like.

The term “alkaryl” refers to an aryl group with an alkyl substituent,and the term “aralkyl” refers to an alkyl group with an arylsubstituent, wherein “aryl” and “alkyl” are as defined above. Preferredalkaryl and aralkyl groups contain 6 to 24 carbon atoms, andparticularly preferred alkaryl and aralkyl groups contain 6 to 16 carbonatoms. Alkaryl groups include, for example, p-methylphenyl,2,4-dimethylphenyl, p-cyclohexylphenyl, 2,7-dimethylnaphthyl,7-cyclooctylnaphthyl, 3-ethyl-cyclopenta-1,4-diene, and the like.Examples of aralkyl groups include, without limitation, benzyl,2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl,4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl,4-benzylcyclohexylmethyl, and the like. The terms “alkaryloxy” and“aralkyloxy” refer to substituents of the formula —OR wherein R isalkaryl or aralkyl, respectively, as just defined.

The term “acyl” refers to substituents having the formula —(CO)-alkyl,—(CO)-aryl, or —(CO)-aralkyl, and the term “acyloxy” refers tosubstituents having the formula —O(CO)— alkyl, —O(CO)-aryl, or—O(CO)-aralkyl, wherein “alkyl,” “aryl, and “aralkyl” are as definedabove.

The terms “cyclic” and “ring” refer to alicyclic or aromatic groups thatmay or may not be substituted and/or heteroatom-containing, and that maybe monocyclic, bicyclic, or polycyclic. The term “alicyclic” is used inthe conventional sense to refer to an aliphatic cyclic moiety, asopposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic,or polycyclic. The term “acyclic” refers to a structure in which thedouble bond is not contained within a ring structure.

The terms “halo,” “halide,” and “halogen” are used in the conventionalsense to refer to a chloro, bromo, fluoro, or iodo substituent.

“Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 toabout 30 carbon atoms, preferably 1 to about 24 carbon atoms, mostpreferably 1 to about 12 carbon atoms, including linear, branched,cyclic, saturated, and unsaturated species, such as alkyl groups,alkenyl groups, aryl groups, and the like. The term “lower hydrocarbyl”intends a hydrocarbyl group of 1 to 6 carbon atoms, preferably 1 to 4carbon atoms, and the term “hydrocarbylene” intends a divalenthydrocarbyl moiety containing 1 to about 30 carbon atoms, preferably 1to about 24 carbon atoms, most preferably 1 to about 12 carbon atoms,including linear, branched, cyclic, saturated and unsaturated species.The term “lower hydrocarbylene” intends a hydrocarbylene group of 1 to 6carbon atoms. “Substituted hydrocarbyl” refers to hydrocarbylsubstituted with one or more substituent groups, and the terms“heteroatom-containing hydrocarbyl” and “heterohydrocarbyl” refer tohydrocarbyl in which at least one carbon atom is replaced with aheteroatom. Similarly, “substituted hydrocarbylene” refers tohydrocarbylene substituted with one or more substituent groups, and theterms “heteroatom-containing hydrocarbylene“and heterohydrocarbylene”refer to hydrocarbylene in which at least one carbon atom is replacedwith a heteroatom. Unless otherwise indicated, the term “hydrocarbyl”and “hydrocarbylene” are to be interpreted as including substitutedand/or heteroatom-containing hydrocarbyl and hydrocarbylene moieties,respectively.

The term “heteroatom-containing” as in a “heteroatom-containinghydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbylmolecular fragment in which one or more carbon atoms is replaced with anatom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus orsilicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that isheteroatom-containing, the term “heterocyclic” refers to a cyclicsubstituent that is heteroatom-containing, the terms “heteroaryl” andheteroaromatic” respectively refer to “aryl” and “aromatic” substituentsthat are heteroatom-containing, and the like. It should be noted that a“heterocyclic” group or compound may or may not be aromatic, and furtherthat “heterocycles” may be monocyclic, bicyclic, or polycyclic asdescribed above with respect to the term “aryl.” Examples of heteroalkylgroups include alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylatedamino alkyl, and the like. Non-limiting examples of heteroarylsubstituents include pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl,indolyl, pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., andexamples of heteroatom-containing alicyclic groups are pyrrolidino,morpholino, piperazino, piperidino, etc.

As used herein, the terms “substrate” or “organic substrate” areintended to connote both discrete small molecules (sometimes describedas “organic compounds”) and oligomers and polymers containing such“aromatic moieties.” The term “aromatic moieties” is intended to referto those portions of the compounds, pre-polymers (i.e., monomericcompounds capable of polymerizing), oligomers, or polymers having atleast one of the indicated aromatic structure. Where shown asstructures, the moieties contain at least that which is shown, as wellas containing further functionalization, substituents, or both,including but not limited to the functionalization described as “Fn”herein.

By “substituted” as in “substituted hydrocarbyl,” “substituted alkyl,”“substituted aryl,” and the like, as alluded to in some of theaforementioned definitions, is meant that in the hydrocarbyl, alkyl,aryl, heteroaryl, or other moiety, at least one hydrogen atom bound to acarbon (or other) atom is replaced with one or more non-hydrogensubstituents. Examples of such substituents include, without limitation:functional groups referred to herein as “Fn,” such as halo (e.g., F, Cl,Br, I), hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy, C₂-C₂₄alkynyloxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl(including C₁-C₂₄ alkylcarbonyl (—CO-alkyl) and C₆-C₂₄ arylcarbonyl(—CO-aryl)), acyloxy (—O-acyl, including C₂-C₂₄ alkylcarbonyloxy(—O—CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (—O—CO-aryl)), C₂-C₂₄alkoxycarbonyl ((CO)—O-alkyl), C₆-C₂₄ aryloxycarbonyl (—(CO)—O-aryl),halocarbonyl (—CO)—X where X is halo), C₂-C₂₄ alkylcarbonato(—O—(CO)—O-alkyl), C₆-C₂₄ arylcarbonato (—O—(CO)—O-aryl), carboxy(—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH₂), mono-(C₁-C₂₄alkyl)-substituted carbamoyl (—(CO)NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄alkyl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₁-C₂₄haloalkyl)-substituted carbamoyl (—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄haloalkyl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C₅-C₂₄ aryl)substitutedcarbamoyl (—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄ alkyl), N—(C₅-C₂₄aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH₂), mono-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C₅-C₂₄aryl)-substituted thiocarbamoyl (—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄alkyl), N—(C₅-C₂₄ aryl)-substituted thiocarbamoyl, carbamido(—NH—(CO)—NH₂), cyano (—C≡N), cyanato (—O—C═N), thiocyanato (—S—C═N),formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH₂), mono-(C₁-C₂₄alkyl)-substituted amino, di-(C₁-C₂₄ alkyl)-substituted amino,mono-(C₅-C₂₄ aryl)substituted amino, di-(C₅-C₂₄ aryl)-substituted amino,C₁-C₂₄ alkylamido (—NH—(CO)-alkyl), C₆-C₂₄ arylamido (—NH—(CO)-aryl),imino (—CR═NH where R=hydrogen, C₁-C₂₄ alkyl, C5-C24 aryl, C₆-C₂₄alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (—CR═N(alkyl), whereR=hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl,etc.), arylimino (—CR═N(aryl), where R=hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), nitro (—NO₂), nitroso(—NO), sulfo (—SO₂OH), sulfonate(SO₂O—), C₁-C₂₄ alkylsulfanyl (—S-alkyl;also termed “alkylthio”), C₅-C₂₄ arylsulfanyl (—S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (—(SO)-alkyl), C₅-C₂₄ arylsulfinyl(—(SO)-aryl), C₁-C₂₄ alkylsulfonyl (—SO₂-alkyl), C₁-C₂₄monoalkylaminosulfonyl-SO₂—N(H) alkyl), C₁-C₂₄dialkylaminosulfonyl-SO₂—N(alkyl)₂, C₅-C₂₄ arylsulfonyl (—SO₂-aryl),boryl (—BH₂), borono (—B(OH)₂), boronato (—B(OR)₂ where R is alkyl orother hydrocarbyl), phosphono (—P(O)(OH)₂), phosphonato (—P(O)(O)₂),phosphinato (P(O)(O—)), phospho (—PO₂), and phosphine (—PH₂); and thehydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, morepreferably C₁-C₆ alkyl), C₂-C₂₄ alkenyl (preferably C₂-C₁₂ alkenyl, morepreferably C₂-C₆ alkenyl), C₂-C₂₄ alkynyl (preferably C₂-C₁₂ alkynyl,more preferably C2-C6 alkynyl), C₅-C₂₄ aryl (preferably C₅-C₂₄ aryl),C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl(preferably C₆-C₁₆ aralkyl). Within these substituent structures, the“alkyl,” “alkylene,” “alkenyl,” “alkenylene,” “alkynyl,” “alkynylene,”“alkoxy,” “aromatic,” “aryl,” “aryloxy,” “alkaryl,” and “aralkyl”moieties may be optionally fluorinated or perfluorinated. Additionally,reference to alcohols, aldehydes, amines, carboxylic acids, ketones, orother similarly reactive functional groups also includes their protectedanalogs. For example, reference to hydroxy or alcohol also includesthose substituents wherein the hydroxy is protected by acetyl (Ac),benzoyl (Bz), benzyl (Bn, Bnl), β-Methoxyethoxymethyl ether (MEM),dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl](DMT), methoxymethylether (MOM), methoxytrityl [(4-methoxyphenyl)diphenylmethyl, MMT),p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl (Piv),tetrahydropyranyl (THP), tetrahydrofuran (THF), trityl (triphenylmethyl,Tr), silyl ether (most popular ones include trimethylsilyl (TMS),tert-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), andtriisopropylsilyl (TIPS) ethers), ethoxyethyl ethers (EE). Reference toamines also includes those substituents wherein the amine is protectedby a BOC glycine, carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz orMeOZ), tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC),acetyl (Ac), benzoyl (Bz), benzyl (Bn), carbamate, p-methoxybenzyl(PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts)group, or sulfonamide (Nosyl & Nps) group. Reference to substituentcontaining a carbonyl group also includes those substituents wherein thecarbonyl is protected by an acetal or ketal, acylal, or diathane group.Reference to substituent containing a carboxylic acid or carboxylategroup also includes those substituents wherein the carboxylic acid orcarboxylate group is protected by its methyl ester, benzyl ester,tert-butyl ester, an ester of 2,6-disubstituted phenol (e.g.2,6-dimethylphenol, 2,6-diisopropylphenol, 2,6-di-tert-butylphenol), asilyl ester, an orthoester, or an oxazoline. Preferred substituents arethose identified herein as not or less affecting the silylationchemistries, for example, including those substituents comprisingalkyls; alkoxides, aryloxides, aralkylalkoxides, protected carbonylgroups; aryls optionally substituted with F, Cl, —CF₃; epoxides; N-alkylaziridines; cis- and trans-olefins; acetylenes; pyridines, primary,secondary and tertiary amines; phosphines; and hydroxides.

By “functionalized” as in “functionalized hydrocarbyl,” “functionalizedalkyl,” “functionalized olefin,” “functionalized cyclic olefin,” and thelike, is meant that in the hydrocarbyl, alkyl, aryl, heteroaryl, olefin,cyclic olefin, or other moiety, at least one hydrogen atom bound to acarbon (or other) atom is replaced with one or more functional groupssuch as those described herein and above. The term “functional group” ismeant to include any functional species that is suitable for the usesdescribed herein. In particular, as used herein, a functional groupwould necessarily possess the ability to react with or bond tocorresponding functional groups on a substrate surface.

In addition, the aforementioned functional groups may, if a particulargroup permits, be further substituted with one or more additionalfunctional groups or with one or more hydrocarbyl moieties such as thosespecifically enumerated above. Analogously, the above-mentionedhydrocarbyl moieties may be further substituted with one or morefunctional groups or additional hydrocarbyl moieties such as thosespecifically enumerated.

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, the phrase “optionally substituted” means that anon-hydrogen substituent may or may not be present on a given atom, and,thus, the description includes structures wherein a non-hydrogensubstituent is present and structures wherein a non-hydrogen substituentis not present.

As used herein, the term “silylating” refers to the forming ofcarbon-silicon bonds, generally in a position previously occupied by acarbon-hydrogen bond, generally a non-activated C—H bond. Silylating maybe seen as coupling of a C—H and Si—H bond to form a C—Si bond. Theability to replace directly a C—H bond with a C—Si bond, under theconditions described herein, is believed to be unprecedented.

As used herein, the term “substantially free of a transition-metalcompound” is intended to reflect that the system is effective for itsintended purpose of silylating terminal alkyne C—H bonds under therelatively mild conditions described herein, even in the absence of anyexogenous (i.e., deliberately added or otherwise) transition-metalcatalyst(s). While certain embodiments provide that transition metals,including those capable of catalyzing silylation reactions, may bepresent within the systems or methods described herein at levelsnormally associated with such catalytic activity (for example, in thecase where the substrates comprise metallocenes), the presence of suchmetals (either as catalysts or spectator compounds) is not required andin many cases is not desirable. As such, in preferred embodiments, thesystem and methods are “substantially free of transition-metalcompounds.” Unless otherwise stated, then, the term “substantially freeof a transition-metal compound” is defined to reflect that the totallevel of transition metal within the silylating system, independently orin the presence of organic substrate, is less than about 5 ppm, asmeasured by ICP-MS as described in Example 2.1.2, Table 2 below. Whenexpressly stated as such, additional embodiments also provide that theconcentration of transition metals is less than about 10 wt %, 5 wt %, 1wt %, 100 ppm, 50 ppm, 30 ppm, 25 ppm, 20 ppm, 15 ppm, 10 ppm, or 5 ppmto about 1 ppm or 0 ppm. As used herein, the term “transition metal” isdefined to include d-block elements, for example Ag, Au, Co, Cr, Rh, Ir,Fe, Ru, Os, Ni, Pd, Pt, Cu, Zn, or combinations thereof. In furtherspecific independent embodiments, the concentration of Ni, as measuredby ICP-MS, is less than 25 ppm, less than 10 ppm, less than 5 ppm, orless than 1 ppm.

While it may not be necessary to limit the system's exposure to waterand oxygen, in some embodiments, the chemical systems and the methodsare done in an environment substantially free of water, oxygen, or bothwater and oxygen. In other embodiments, air and/or water are present.Unless otherwise specified, the term “substantially free of water”refers to levels of water less than about 500 ppm and “substantiallyfree of oxygen” refers to oxygen levels corresponding to partialpressures less than 1 torr. Where stated, additional independentembodiments may provide that “substantially free of water” refers tolevels of water less than 1.5%, 1%, 0.5%, 1000 ppm, 500 ppm, 250 ppm,100 ppm, 50 ppm, 10 ppm, or 1 ppm and “substantially free of oxygen”refers to oxygen levels corresponding to partial pressures less than 50torr, 10 torr, 5 torr, 1 torr, 500 millitorr, 250 millitorr, 100millitorr, 50 millitorr, or 10 millitorr. In the General Proceduredescribed herein, deliberate efforts were made to exclude both water andoxygen, unless otherwise specified.

The following listing of Embodiments is intended to complement, ratherthan displace or supersede, the previous descriptions.

Embodiment 1

A method comprising contacting at least one organic substrate comprisinga terminal alkynyl C—H bond, with a mixture of at least one organosilaneand an alkali metal hydroxide (or alkoxide or hydride), under conditionssufficient to form a silylated terminal alkynyl moiety in thesubstantially absence of transition-metal compounds. Relatedly, thismethod also comprises operating in the substantial absence of transitionmetal compounds, or other electromagnetic or thermal initiation orpropagation.

Embodiment 2

The method of Embodiment 1, wherein the transition-metal compounds arepresent at less than 1 ppm, relative to the weight of the total system.

Embodiment 3

The method of Embodiment 1 or 2, wherein at least one organosilanecomprises an organosilane of Formula (I), Formula (II), or Formula(III):

(R)_(4-m)Si(H)_(m)  (I)

(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)

R—[—SiH(R)—O—]_(n)—R  (III)

where: m and p are are independently 1, 2, or 3; q is 0, 1, 2, 3, 4, 5,or 6; r is 0 or 1; n is 10 to 100; and each R is independently halo(e.g., F, Br, Cl, I)(provided at least one R is contains carbon),optionally substituted C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted C₁₋₁₂ alkenyl or heteroalkenyl, optionally substituted C₁₋₁₂alkynyl or heteroalkynyl, optionally substituted C₅₋₂₀ aryl or C₃₋₂₀heteroaryl, optionally substituted C₆₋₃₀ alkaryl or heteroalkaryl,optionally substituted C₅₋₃₀ aralkyl or heteroaralkyl, optionallysubstituted —O—C₁₋₁₂ alkyl or heteroalkyl, optionally substituted—O—C₅₋₂₀ aryl or —O—C₃₋₂₀ heteroaryl, optionally substituted —O—C₅₋₃₀alkaryl or heteroalkaryl, or optionally substituted —O—C₅₋₃₀ aralkyl orheteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato, isocyanate,thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl,siloxazanyl, boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.In some embodiments for Formula (II), q is 0. In some embodiments forFormula (II), r is 0. Any of the silanes described in this disclosureare also considered separate embodiments when used in these methods orsystems.

Embodiment 4

The method of claim 3, wherein the organosilane is (R)₃SiH, (R)₂SiH₂, or(R)SiH₃. In some of these embodiments, R is independently alkoxy, alkyl,alkenyl, aryl, aryloxy, heteroaryl, aralkyl, or heteroaralkyl.

Embodiment 5

The method of any one of Embodiments 1 to 4, wherein the alkali metalhydroxide is sodium hydroxide (NaOH) (or the alkali metal alkoxide issodium alkoxide).

Embodiment 6

The method of Embodiment 5, wherein the organosilane is EtMe₂SiH,PhMe₂SiH, BnMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂, (EtO)₃SiH, Me₂(pyridinyl)SiH,or Me₃Si—SiMe₂H.

Embodiment 7

The method of any one of Embodiments 1 to 4, wherein the alkali metalhydroxide is potassium hydroxide (KOH) (or the alkali metal alkoxide ispotassium alkoxide).

Embodiment 8

The method of Embodiment 7, wherein the organosilane is EtMe₂SiH,PhMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂, (i-Pr)₃SiH, or (i-Pr)₂(pyridinyl)SiH.

Embodiment 9

The method of any one of Embodiments 1 to 8, wherein the organicsubstrate comprising the terminal alkynyl C—H bond has a formula:

R¹—C≡C—H,

where R¹ comprises H, an optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroalkyl, optionallysubstituted heteroaryl, optionally substituted aralkyl, optionallysubstituted heteroaralkyl, or optionally substituted metallocene.

Embodiment 10

The method of Embodiment 9, wherein R¹ is or comprises an optionallysubstituted linear alkyl, an optionally substituted branched alkyl, oran optionally substituted cycloalkyl.

Embodiment 11

The method of Embodiment 9, wherein R¹ is or comprises an optionallysubstituted linear alkenyl, an optionally substituted branched alkenyl,or an optionally substituted cycloalkenyl

Embodiment 12

The method of Embodiment 9, wherein R¹ is or comprises an optionallysubstituted linear heteroalkyl, an optionally substituted branchedheteroalkyl, or an optionally substituted heterocycloalkyl.

Embodiment 13

The method of Embodiment 9, wherein R¹ is or comprises an optionallysubstituted aryl, an optionally substituted aralkyl, optionallysubstituted heteroaryl, or an optionally substituted heteroaralkyl.

Embodiment 14

The method of Embodiment 13, wherein R¹ is or comprises an optionallysubstituted benzene, biphenyl, naphthalene, or anthracene ringstructure.

Embodiment 15

The method of Embodiment 13, wherein R¹ is or comprises an optionallysubstituted furan, pyrrole, thiophene, pyrazole, imidazole, triazole,isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine,pyridazine, pyrimidine, pyrazine, triazone, benzofuran, benzopyrrole,benzothiophene, isobenzofuran, isobenzopyrrole, isobenzothiophene,indole, isoindole, indolizine, indazole, azaindole, benzisoxazole,benzoxazole, quinoline, isoquinoline, cinnoline, quinazoline,naphthyridine, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety.

Embodiment 16

The method of any one of Embodiments 1 to 15, wherein the organicsubstrate comprising the terminal alkynyl C—H bond is polymeric.

Embodiment 17

The method of any one of Embodiments 3 to 16, where m=2, or 3, furthercomprising contacting a second or third organic substrate comprising aterminal alkynyl C—H bond with the first formed silylated terminalalkynyl moiety to form a di- or tri-akynyl cross-coupled silane product.This second (or third) organic substrate can be same or different thanfirst.

Embodiment 18

The method of any one of Embodiments 1 to 17, further comprisingreacting the silylated terminal alkynyl moiety with another unsaturatedmoiety in a [2+2] or [4+2] cycloaddition reaction to form an aromatic,heteroaromatic, cycloalkenyl, or heterocycloalkenyl moiety. Theunsaturated moiety can include alkene, alkyne, azide, nitrile,isocynate, isothiocyanate, carbonyl, amide, urea, etc., and the reactionmay be inter- or intramolecular.

Embodiment 19

The method of any one of Embodiments 1 to 17, further comprisingreacting the silylated terminal alkynyl moiety with a second,unsaturated organic moiety in a cross-metathesis reaction to form adiolefin or polyolefin product. The unsaturated moiety can includealkene, alkyne, azide, nitrile, isocynate, isothiocyanate, carbonyl,amide, urea, etc., and the reaction may be inter- or intramolecularreaction. In some of these embodiments, the metathesis is accomplishedusing a Grubbs-type metathesis reaction catalyst.

Embodiment 20

The method of any one of Embodiments 1 to 17, further comprisingpolymerizing the silylated terminal alkynyl moiety. The silylatedterminal alkynyl moiety may also be copolymerized with other acetylenicor olefinic compounds, by any means, including metathesis and freeradical mechanisms.

Embodiment 21

The method of any one of Embodiments 1 to 17, further comprisingreacting the silylated terminal alkynyl moiety with an organic azide a[3+2]azide-alkyne cycloaddition reaction. This so-called Clickchemistry, includes 1,3-dipolar cycloadditions, may be inter- orintramolecular reaction, and typically involve the use of copper,copper-iron, or ruthenium-containing catalysts.

Embodiment 22

The method of any one of Embodiments 1 to 17, further comprisinghydrogenating the silylated terminal alkynyl moiety. Certain otherembodiments include the reaction of the silylated terminal alkynylmoiety with water, alcohols, hydrogen cyanide, hydrogen chloride,dihalogen, or carboxylic acids to give corresponding vinyl or carbonylcompounds.

Embodiment 23

The method of any one of Embodiments 1 to 20, further comprisingremoving the silyl group originally added to the terminal alkynyl C—Hbond, such the the added silyl group was used as a blocking or directinggroup for other transformations in the substrate.

Embodiment 24

The method of any one of Embodiments 1 to 20, further comprisingreacting silylated terminal alkynyl moiety with an aromatic halidecompound under conditions sufficient to form an alkynyl-arene linkage;e.g., using Pd(PPh₃)₂Cl₂/CuI catalysts with aromatic bromo or iodocompounds.

Embodiment 25

The method of any one of Embodiments 1 to 17, further comprisingreacting the silylated terminal alkynyl moiety with an N-halosuccinimidein the presence of a cationic gold catalyst to produce a terminalalkynyl halide, where halo is preferably bromo or iodo.

Embodiment 26

The method of any one of Embodiments 1 to 20, wherein the at least oneorganosilane comprises an optionally substituted C₁₋₁₂ alkenyl orheteroalkenyl, such that the silylated terminal alkynyl moiety comprisesa silicon bonded optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl,the method further comprising reacting the silylated terminal alkynylmoiety with an alcohol and a catalyst under conditions to result in theintramolecular allylation of the silylated terminal alkynyl moiety.

Embodiment 27

The method of any one of Embodiments 1 to 20, wherein the at least oneorganosilane comprises a 2-pyridinyl group (as typified herein using(Me)₂(pyridinyl)SiH or (i-Pr)₂(pyridinyl)SiH), the method furthercomprising reacting the silylated terminal alkynyl moiety with a coppercarbomagnesation catalyst and an optionally substituted aryl oroptionally substituted heteroaryl magnesium complex under conditionssufficient to carbomagnesate the silylated terminal alkynyl moiety.

Embodiment 28

The method of Embodiment 27, further comprising reacting thecarbomagnesated silylated terminal alkynyl moiety with an optionallysubstituted aryl iodide or optionally substituted heteroaryl iodide inthe presence of a palladium catalyst to form a trisubstituted silylatedolefin.

Embodiment 29

The method of Embodiment 28, further comprising reacting thetrisubstituted silylated olefin with BCl₃ and pinacol under conditionssufficient to borodesilylate the compound, and optionally reacting theborodesilylated compound with a second optionally substituted aryliodide or optionally substituted heteroaryl iodide under conditionssuitable to cross-couple the resulting C—B bond and the secondoptionally substituted aryl iodide or optionally substituted heteroaryliodide.

Embodiment 30

A system for silylating an organic substrate comprising a terminalalkynyl C—H bond, said system comprising or consisting essentially of amixture of (a) at least one organosilane and (b) an alkali metalhydroxide (or in some cases, alkali metal alkoxide or hydride), and (c)at least one substrate. Such systems may be substantially free oftransition-metal compounds. Such systems may also contain a silylatedproduct derived from the at least one organosilane and the terminalalkyne.

Embodiment 31

The system of Embodiment 30, wherein the transition-metal compound ispresent at less than 10 ppm, relative to the weight of the total system.

Embodiment 32

The system of Embodiment 30 or 31, wherein at least one organosilanecomprises an organosilane of Formula (I), Formula (II), or Formula(III):

(R)_(4-m)Si(H)_(m)  (I)

(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)

R—[—SiH(R)—O—]_(n)—R  (III)

where: m and p are are independently 1, 2, or 3; q is 0, 1, 2, 3, 4, 5,or 6; r is 0 or 1; n is 10 to 100; and each R is independently halo(e.g., F, Br, Cl, I)(provided at least one R is contains carbon),optionally substituted C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted C₁₋₁₂ alkenyl or heteroalkenyl, optionally substituted C₁₋₁₂alkynyl or heteroalkynyl, optionally substituted C₅₋₂₀ aryl or C₃₋₂₀heteroaryl, optionally substituted C₆₋₃₀ alkaryl or heteroalkaryl,optionally substituted C₅₋₃₀ aralkyl or heteroaralkyl, optionallysubstituted —O—C₁₋₁₂ alkyl or heteroalkyl, optionally substituted—O—C₅₋₂₀ aryl or —O—C₃₋₂₀ heteroaryl, optionally substituted —O—C₅₋₃₀alkaryl or heteroalkaryl, or optionally substituted —O—C₅₋₃₀ aralkyl orheteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato, isocyanate,thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl,siloxazanyl, boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.In some embodiments for Formula (II), q is 0. In some embodiments forFormula (II), r is 0.

Embodiment 33

The system of Embodiment 32, wherein the organosilane is (R)₃SiH or(R)₂SiH₂, where R is independently alkoxy, alkyl, alkenyl, aryl,aryloxy, heteroaryl, aralkyl, or heteroaralkyl.

Embodiment 34

The system of any one of Embodiments 30 to 33, wherein the alkali metalhydroxide is sodium hydroxide (NaOH) (or the alkali metal alkoxide issodium alkoxide).

Embodiment 35

The system of Embodiment 34, wherein the organosilane is EtMe₂SiH,PhMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂, PhMe₂SiH, BnMe₂SiH, (Me)₂(pyridinyl)SiH,(EtO)₃SiH, or Me₃Si—SiMe₂H.

Embodiment 36

The system of any one of Embodiments 30 to 33, wherein the alkali metalhydroxide is potassium hydroxide (KOH) (or the alkali metal alkoxide ispotassium alkoxide).

Embodiment 37

The system of Embodiment 36, wherein the organosilane is EtMe₂SiH,PhMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂, (i-Pr)₃SiH, or (i-Pr)₂(pyridinyl)SiH.

Embodiment 38

The system of any one of Embodiments 30 to 37, wherein the organicsubstrate comprising the terminal alkynyl C—H bond has a formula:

R¹—C≡C—H,

where R¹ comprises H, an optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, optionallysubstituted aryl, optionally substituted heteroalkyl, optionallysubstituted heteroaryl, optionally substituted aralkyl, optionallysubstituted heteroaralkyl, or optionally substituted metallocene.

Embodiment 39

The system of Embodiment 38, wherein R¹ is or comprises an optionallysubstituted linear alkyl, an optionally substituted branched alkyl, oran optionally substituted cycloalkyl.

Embodiment 40

The system of Embodiment 38, wherein R¹ is or comprises an optionallysubstituted linear heteroalkyl, an optionally substituted branchedheteroalkyl, or an optionally substituted heterocycloalkyl.

Embodiment 41

The system of Embodiment 38, wherein R¹ is or comprises an optionallysubstituted aryl, an optionally substituted aralkyl, optionallysubstituted heteroaryl, or an optionally substituted heteroaralkyl.

Embodiment 42

The system of Embodiment 41, wherein R¹ is or comprises an optionallysubstituted benzene, biphenyl, naphthalene, or anthracene ring structure

Embodiment 43

The system of Embodiment 39, wherein R¹ is or comprises an optionallysubstituted furan, pyrrole, thiophene, pyrazole, imidazole, triazole,isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine,pyridazine, pyrimidine, pyrazine, triazone, benzofuran, benzopyrrole,benzothiophene, isobenzofuran, isobenzopyrrole, isobenzothiophene,indole, isoindole, indolizine, indazole, azaindole, benzisoxazole,benzoxazole, quinoline, isoquinoline, cinnoline, quinazoline,naphthyridine, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety.

Embodiment 44

The system of any one of Embodiments 30 to 43, wherein the organicsubstrate comprising the terminal alkynyl C—H bond is polymeric.

Embodiment 45

The system of any one of Embodiments 30 to 44, comprising at least twodifferent organosilanes.

Embodiment 46

The system of any one of Embodiments 30 to 45, comprising at least twodifferent organic substrates, each comprising a terminal alkynyl C—Hbond.

EXAMPLES

The following Examples are provided to illustrate some of the conceptsdescribed within this disclosure. While each Example is considered toprovide specific individual embodiments of composition, methods ofpreparation and use, none of the Examples should be considered to limitthe more general embodiments described herein.

In the following examples, efforts have been made to ensure accuracywith respect to numbers used (e.g. amounts, temperature, etc.) but someexperimental error and deviation should be accounted for. Unlessindicated otherwise, temperature is in degrees C., pressure is at ornear atmospheric.

Example 1 General Observations of Experimental Data

Initial investigations with the silylation of acetylene 1(prop-2-ynyl-cyclohexane, FIG. 2) with Et₃SiH were conducted underreactions conditions used for the silylation of heteroarenes usingKOt-Bu-catalyzed C(sp²)-H silylation conditions. In this case, theobserved ethynylsilane 2a was obtained in good yield, along with 9% ofundesired alkyne migration product 1-iso (FIG. 2, entry 1). NaOt-Bu(entry 2) and LiOt-Bu (entry 3) were inferior catalysts, and commonorganic bases (entries 4-6) also gave poor results. Surprisingly, themilder KOH was superior to KOt-Bu at 10 mol % catalyst loading (entry7). Moving from Et₃SiH to PhMe₂SiH permitted the reaction to occur atambient temperature while still maintaining high yields (entry 8). Insharp contrast to the previously reported heteroarene C—H silylationprotocol wherein a strong potassium base is crucial to the reactivity,inexpensive and mild NaOH proved to be the ideal catalyst for thesilylation of 1 affording 2b in 93% yield (entry 9). LiOH (entry 10) didnot catalyze the reaction (see Table 1, below).

Varying the steric and electronic properties of the hydrosilane partner(FIG. 2) showed that a number of new ethynylsilanes could be produced,including those with synthetically versatile hydride-(2e and 2f),benzyldimethyl-(2g), triisopropyl-(2h), triethoxy-(2i), and2-dialkylpyridyl-(2j and 2k) substituents on silicon (FIG. 2 b). LabileSi—Si bonds that are cleaved under transition metal catalysis or in thepresence of nucleophiles or acids are also well tolerated, furnishing 2lin 95% yield. This appears to be the broadest scope of mono- anddihydrosilanes reported to date in the C—H silylation field.

A wide variety of alkynes were shown to be reactive, including thosebearing electron-rich and electron-deficient aryl (4a-j), heteroaryl(4k-m), and alkyl (4o-y) groups (FIG. 3). Sensitive functional groupssuch as aryl halides (4b-d), an alkyl chloride (4v), and cyclopropane(4r) were tolerated without any undesired side reactions. Substratesbearing acidic functionalities such as propargylamine (3w) and propargylalcohol (3x) also reacted well, providing 4w and bis-silylated 4xrespectively in high yields. Unprecedented catalyticcross-dehydrogenative silylation of N-heterocyclic systems, such aspyridine 3m, and imidazole 3k, also successful gave the correspondingsilylated building blocks 4m and 4k. Substrates containing C—H bondsthat are susceptible to KOt-Bu-catalyzed silylation, or those that areengaged under other C—H functionalization chemistries, such as anisole3g, thiophene 3y, toluene 3f, propargyl ether 3q, and benzene derivative3t, all reacted with excellent chemoselectivity (>99:1) at the terminalalkyne C—H bond without any observed C(sp²)-H or C(sp³)-H silylation.The complete suppression of Minisci-type radical functionalizations(e.g., pyridine 3m), and electrophilic substitution reactions (e.g.,electron-rich system 3n and ferrocene 3h) suggest that a novel C—Hfunctionalization mechanism is operative. The clean reaction profileswith these substrates demonstrated the unique benefits of catalysis byNaOH compared with transition metal-catalyzed methods and classicalstoichiometric deprotonation strategies.

This alkali metal hydroxide-catalyzed silylation reaction scaled wellwithout loss of catalyst activity as demonstrated by the multi-gramsynthesis of 4s (FIG. 4A) and can be applied to challenging problems inorganic synthesis, materials science, and late stage pharmaceuticalderivatization. For example, successful experiments showed thatsymmetrical aliphatic or aromatic diynes can be bis-silylated (5b and6b) or selectively mono-functionalized (5a and 6a) generatingsynthetically valuable, orthogonally activated alkyne building blocks(FIG. 4B). The catalyst's ability to differentiate the alkynes leadingto mono-substituted 5a was especially surprising and not presentlyunderstood given the lack of electronic communication between theidentical alkynes in the starting material. The use of dihydrosilanesallowed for the preparation of symmetrical diethynylsilanes by doubleC(sp)-H silylation (FIGS. 4C, 7). Simultaneously reacting two differentterminal alkynes and a dialkylsilane in a three-component couplingreaction produced unsymmetrical diethynylsilane 8 in 76% yield, alongwith 10% of 7 (formed by homocoupling of 1) and <5% yield of thehomocoupled cyclopropylacetylene product. By taking advantage of therate differences between the alkyne partners, this non-statisticalproduct distribution favouring the cross product was obtained (seeExample 3.4). These silanes are precursors to functionalized siloles,polysiloles or silole-co-polymers, and further embodiments of thepresent invention provide for the further reactions of the silylatedproducts to this end. Moreover, the hydroxide-catalyzed silylationprotocol was employed in the first catalytic installation of theversatile 2-dimethylsilylpyridyl directing group furnishing 2k in 78%yield, which can be advanced to highly substituted olefins (FIG. 4D).Again, further embodiments of the present invention provide for thefurther reactions of the silylated products to this end.

Sila-drug analogues are garnering increased attention from medicinalchemists because they can offer improved pharmacokinetic propertiesrelative to the all-carbon substance. Moreover, the installedorganosilicon moiety can serve as a functional group handle forsubsequent elaboration or as an easily-removable protecting group.Again, further embodiments of the present invention provide for thefurther reactions of the silylated products to this end. To evaluate thepresent methods for such late-stage C—H functionalization applications,the pharmaceutical substances pargyline and mestranol were subjected tothe catalytic silylation conditions, successfully providing novelsila-drug analogues 9 and 10 in 96% and 82% yield respectively (FIG.4E).

The underlying mechanistic details of the alkali metal hydroxide,alkoxide, or hydride catalyzed silylation are not well understood atthis point. A C—H deprotonation process is conceivable, but raisesquestions of thermodynamics (i.e., pKa difference between thedeprotonating base and the C(sp)-H bond), the mechanism of catalystturnover, and the nature of the reactive Si species. Preliminary studiesfurther suggest that the mechanism is distinct from previously disclosedC(sp)-H silylation reactions including KOt-Bu-catalyzed C(sp²)-Hsilylation of heteroarenes. This is based on the results from radicaltrapping and countercation chelation studies (see Example 2.1.3), theimproved yields and greatly expanded hydrosilane and substrate scopecompared to previous reports, and the fact that sodium hydroxide showsgreatly improved activity compared to precious metal species,Lewis-acids, and KOt-Bu. With respect to the latter, attempting toemploy KOt-Bu as the catalyst for the C(sp)-H coupling surprisinglyfailed in the majority of cases evaluated (see FIG. 6). Moreover, astriking difference in reactivity between KOH and NaOH, which differonly in the identity of the countercation, was observed. The apparentnon-innocence of the cation cannot be easily rationalized by solubility,aggregation state, or basicity arguments given the lack of discerniblereactivity trends in the substrates investigated under identicalconditions (FIG. 5). These data suggest that simple alkali metalcations—either as additives or as catalyst countercations—play animportant role in the discovery and development of novel catalyticprocesses.

Example 2 General Information

Unless otherwise stated, reactions were performed in oven-driedbrand-new Fisherbrand scintillation vials in a nitrogen filled glove boxor in flame-dried Schlenk flasks under argon connected on a Schlenk lineusing dry, degassed solvents and brand-new stirring bars. Solvents weredried by passage through an activated alumina column under argon.Reaction progress was monitored by thin-layer chromatography (TLC) orGC-FID analyses. TLC was performed using E. Merck silica gel 60 F254precoated glass plates (0.25 mm) and visualized by UV fluorescencequenching, phosphomolybdic acid, or KMnO₄ staining. Silicycle SiliaFlashP60 Academic Silica gel (particle size 40-63 nm) was used for flashchromatography. ¹H NMR spectra were recorded on a Varian Inova 500 MHzspectrometer in CDCl₃ or THF-d8 and are reported relative to residualsolvent peak at δ 7.26 ppm or δ 3.58 ppm respectively. ¹³C NMR spectrawere recorded on a Varian Inova 500 MHz spectrometer (126 MHz) in CDCl₃or THF-d8 and are reported relative to residual solvent peak at δ 77.16ppm or δ 67.21 ppm respectively. Data for ¹H NMR are reported asfollows: chemical shift (δ ppm) (multiplicity, coupling constant (Hz),integration). Multiplicities are reported as follows: s=singlet,d=doublet, t=triplet, q=quartet, p=pentet, sept=septet, m=multiplet, brs=broad singlet, br d=broad doublet, app=apparent. Data for ¹³C NMR arereported in terms of chemical shifts (δ ppm). IR spectra were obtainedon a Perkin Elmer Spectrum BXII spectrometer using thin films depositedon NaCl plates and reported in frequency of absorption (cm⁻¹). GC-FIDanalyses were obtained on an Agilent 6890N gas chromatograph equippedwith a HP-5 (5%-phenyl)-methylpolysiloxane capillary column (Agilent).GC-MS analyses were obtained on an Agilent 6850 gas chromatographequipped with a HP-5 (5%-phenyl)-methylpolysiloxane capillary column(Agilent). High resolution mass spectra (HRMS) were acquired from theCalifornia Institute of Technology Mass Spectrometry Facility. ICP-MSanalysis was conducted at the California Institute of Technology MassSpectrometry Facility.

Silanes were purchased from Aldrich and distilled before use. KOt-Bu waspurchased from Aldrich (sublimed grade, 99.99% trace metals basis) andused directly. KOH was purchased from Aldrich (semiconductor grade,pellets, 99.99% trace metals basis) and was pulverized (mortar andpestle) and heated (150° C.) under vacuum prior to use. NaOH waspurchased from Aldrich (semiconductor grade, pellets, 99.99% tracemetals basis) and was pulverized (mortar and pestle) and heated (150°C.) under vacuum prior to use. Alkyne substrates were purchased fromAldrich, TCI, or Acros.

Example 2.1 Reaction Optimizations, Trace Metal Analysis, andPreliminary Mechanistic Investigations Example 2.1.1 ReactionOptimization

Procedure for reaction condition optimization: In a nitrogen-filledglovebox, catalyst and alkyne 1a (0.1 mmol, 1 equiv) were added to a 2dram scintillation vial equipped with a magnetic stirring bar. Next,hydrosilane and solvent (0.1 mL) were added. The vial was sealed and themixture was stirred at the indicated temperature for the indicated time.The vial was then removed from the glovebox, diluted with diethyl ether(1 mL), and concentrated under reduced pressure. The yield wasdetermined by ¹H NMR or GC analysis of the crude mixture using aninternal standard.

TABLE 1 Condition optimization of direct C(sp)—H silylation.

entry catalyst [Si]—H solvent T, °C. time, h yield 2a yield 1-iso 1KOt-Bu (20 mol%) Et₃SiH — 85 72   22% 60% 2 KOt-Bu (20 mol%) Et₃SiH THF85 72   94%  1% 3 KOt-Bu (20 mol%) Et₃SiH 1,4-dioxane 85 72   88% — 4KOt-Bu (20 mol%) Et₃SiH DME 85 72 >99% — 5 KOt-Bu (20 mol%) Et₃SiH MTBE85 72   30% 53% 6 KOt-Bu (20 mol%) Et₃SiH toluene 85 72   27% 59% 7KOt-Bu (20 mol%) Et₃SiH CyMe 85 72   15% 66% 8 KOt-Bu (20 mol%) Et₃SiHPentane 85 72   13% 74% 9 KOt-Bu (20 mol%) Et₃SiH Mesitylene 85 72   26%56% 10 KOt-Bu (20 mol%) Et₃SiH DCM 85 72 — — 11 KOt-Bu (20 mol%) Et₃SiHEt₂O 85 72   23% 61% 12 KOt-Bu (20 mol%) Et₃SiH 2-Me—THF 85 72   48% 51%13 KOt-Bu (40 mol%) Et₃SiH THF 85 48   89% — 14 KOt-Bu (20 mol%) Et₃SiHTHF 85 48   99% — 15 KOt-Bu (10 mol%) Et₃SiH THF 85 48 >99% — 16 KOt-Bu(5 mol%) Et₃SiH THF 85 48   99% <1% 17 KOt-Bu (1 mol%) Et₃SiH THF 85 48  97%  2% 18 KOt-Bu (10 mol%) Et₃SiH THF 25 48    7% 63% 19 KOt-Bu (10mol%) Et₃SiH THF 55 48   59% 30% 20 KH (20 mol%) Et₃SiH THF 85 72   99%— 21 KHMDS (20 mol%) Et₃SiH THF 85 72   99% <1% 22 NaOt-Bu (20 mol%)Et₃SiH THF 85 72   51% 40% 23 LiOt-Bu (20 mol%) Et₃SiH THF 85 72  <1% 5% 24 DABCO (20 mol%) Et₃SiH THF 85 72  <1% — 25 NaOEt (20 mol%) Et₃SiHTHF 85 72   82% <1% 26 KOEt (20 mol%) Et₃SiH THF 85 72   99% <1% 27NaOAc (20 mol%) Et₃SiH THF 85 72  <1% — 28 KOAc (20 mol%) Et₃SiH THF 8572  <1% — 29 KOMe (20 mol%) Et₃SiH THF 85 72   98% <1% 30 NaOMe (20mol%) Et₃SiH THF 85 72   95%  3% 31 KOt-amyl (20 mol%) Et₃SiH THF 8572 >99% <1% 32 KOH (20 mol%) Et₃SiH THF 85 72   94% <1% 33 K₂CO₃ (20mol%) Et₃SiH THF 85 72  <1% — 34 Cs₂CO₃ (20 mol%) Et₃SiH THF 85 72 — —35 KF (20 mol%) Et₃SiH THF 85 72  <1% — 36 KOt-Bu (10 mol%) Et₃SiH THF85 24   89%  9% 37 KH (10 mol%) Et₃SiH THF 85 24   87% 11% 38 NaOt-Bu(10 mol%) Et₃SiH THF 85 24   46%  2% 39 LiOt-Bu (10 mol%) Et₃SiH THF 8524  <1% — 40 KOEt (10 mol%) Et₃SiH THF 85 24   96%  2% 41 NaOEt (10mol%) Et₃SiH THF 85 24   91% <1% 42 KOMe (10 mol%) Et₃SiH THF 85 24  96%  4% 43 NaOMe (10 mol%) Et₃SiH THF 85 24   83% <1% 44 KOt-Amyl (10mol%) Et₃SiH THF 85 24   91%  6% 45 KOH (10 mol%) Et₃SiH THF 85 24   95% 3% 46 NaOH (10 mol%) Et₃SiH THF 85 24   98% — 47 LiOH (10 mol%) Et₃SiHDME 85 24    3% — 48 Et₃N (10 mol%) Et₃SiH DME 85 48    4% — 49 Pyridine(10 mol%) Et₃SiH DME 85 48    1% — 50 KOH (10 mol%) Et₃SiH (1.0 eq) THF85 48   71% 21% 51 KOH (10 mol%) Et₃SiH (1.5 eq) THF 85 48   92%  6% 52KOH (10 mol%) Et₃SiH (2.0 eq) THF 85 48   93%  6% 53 KOH (10 mol%)Et₃SiH (2.5 eq) THF 85 48   97%  2% 54 KOH (10 mol%) Et₃SiH (3.0 eq) THF85 48   98%  1% 55 KOH (10 mol%) Et₃SiH (3.5 eq) THF 85 48   99%  1% 56KOH (10 mol%) Et₃SiH (4.0 eq) THF 85 48   97%  2% Yields determined byGC analysis of the crude reaction mixture using an internal standard.

The results from Table 1 reveal that there is a high degree oftunability in the reaction conditions for the C(sp)-H silylationreaction. THF, dioxane, and DME all proved to be suitable solvents, withlow amounts of the isomerized starting material produced (Entries 2, 3,4 respectively). Low loadings of catalyst were achieved with KOt-Bu,down to 1 mol %, without significant loss of yield (Entries 15-17). Hightemperatures (85° C.) proved necessary for silylation withtriethylsilane (Entries 15, 18, 19); as seen in the silane screen in thetext, lower temperatures were achieved when employing various othersilanes. The extensive base screen (Entries 20-35) with longer reactiontimes (72 h) showed that there are a number of good catalysts for theC—H silylation reaction. A refined base screen with lower catalystloading (Entries 36-49) revealed that there were still several catalyststhat performed with surprisingly high efficiency, but NaOH proved to bethe most convenient and high-performing catalyst. No product wasobserved in the absence of catalyst, or when LiOt-Bu, NaOAc, KOAc,DABCO, K₂CO₃, Cs₂CO₃, or KF were employed (Entries 39, 27, 28, 24, 33,34, 35 respectively).

Example 2.1.2 Trace Metal Analysis by ICP-MS

ICP-MS Trace Metal Analysis of all the Reaction Components.

To provide further support against involvement of adventitious tracemetal species in the cross-dehydrogenative C(sp)-H silylation catalysis,inductively coupled plasma mass spectrometry was performed on samples ofNaOH, KOH, 3-cyclohexyl-1-propyne starting material, dimethoxyethane(DME) solvent, PhMe₂SiH, and a standard reaction mixture that was rununder optimal conditions in the glove box. The results from quantitativeanalysis revealed that most metal contaminants were present below theinstrument's lowest limit of detection (i.e., in ppt range or lower).Microgram per liter (ppb) quantities of metal contaminants are given inTable 2.

Samples each of NaOH (1000 mg, 99.99% Aldrich), 3-cyclohexyl-1-propyne,PhMe₂SiH, 1,2-dimethoxyethane, and a standard reaction mixture (0.5 mmolscale mixture, prepared following the general procedure with 61.1 mg of3-cyclohexyl-1-propyne, 2 mg of NaOH, 204.4 mg of PhMe₂SiH in 0.5 mL of1,2-dimethoxyethane (DME) and stirred in the glovebox for 48 h.) wereanalyzed.

Each sample was added to a 50 mL DigiTUBE digestion tube (SCP Science)followed by addition of 3.0 mL of Plasma Pure nitric acid (SCP Science)and heating to 75° C. for 36 hours. After digestion, each sample wasdiluted using Milli Q water to 50 mL and subjected to trace metalanalysis. Trace metal concentrations were determined by InductivelyCoupled Plasma—Mass Spectrometry using an Agilent 8800. The sampleintroduction system consisted of a micromist nebulizer, scott type spraychamber and fixed injector quartz torch. A guard electrode was used andthe plasma was operated at 1500 W. Elements were determined insingle-quad mode with either no gas or helium (kinetic energydiscrimination mode) in the collision cell. 33 elements were calibratedusing external standard solutions ranging from 1 to 100 ppb(micrograms/L). Detection limits of trace elements of concern were belowthe 1 ppb standard. In addition Quick Scan data in helium mode data werecalibrated semiquantitatively. LOD indicated that the analyteconcentration is below the instrument's Lowest Limit of Detection.Values are in ppb unless otherwise stated.

TABLE 2 Trace-metal analysis of reactants in the alkyne silylationreaction. Values in ng/g (ppb) Unless Otherwise Stated* 3-cyclohexyl-1,2- Reaction Element NaOH KOH 1-propyne DME PhMe₂SiH Mixture Ti LOD 0.767*  0.324* 0.206*  0.545*  0.059* Co LOD LOD 18.543  LOD LOD LOD CuLOD LOD 10.440  0.069* 3.048 0.116 Zn LOD  0.682* 25.908* 1.787*  0.063*0.320 Zr LOD LOD LOD LOD  0.232* LOD Mo LOD LOD LOD LOD  1.118* LOD RuLOD 21.248  1.576 LOD 41.188  18.692  Rh LOD 0.165 LOD LOD 0.908 LOD PdLOD 1.834 0.612 7.950  7.339 0.612 Ag LOD LOD LOD LOD LOD LOD Re LOD0.156 LOD 0.700  5.835 0.311 Os LOD LOD LOD LOD LOD LOD Ir LOD  0.063* 7.776* 0.253*  2.429* 0.604 Pt LOD 0.406 0.135 0.813  1.490 0.271 AuLOD LOD 0.115 LOD 1.729 1.383 *ppm

Example 2.1.3 Preliminary Mechanistic Experiments

A number of experiments were conducted to gain insight into the reactionmechanism. As a first investigation, experiments were conducted in anattempt to determined whether the silylation reaction was polar orradical in nature. The reactions were performed in the presence of theradical traps TEMPO and galvinoxyl. Neither additive thwarted the alkyneC—H silylation: TEMPO did not inhibit the reaction at 10% loading butlowered the silylation yield at 300% loading; the effect of galvinoxylon the reaction conditions moving from 10 mol % to 300 mol % additivewas unexpected and not presently understood (Scheme 1).

The effect of potassium and sodium chelating agents in the silylationreaction was also studied to investigate the importance of the cation inthe catalysis. When 18-crown-6 and 15-crown-5 were added to reactionsusing KOH and NaOH as the catalysts respectively, quantitativesilylation was still observed when using triethylsilane as the siliconpartner, suggesting either that ineffective chelation of the metal ionhad occurred or that the cation was not necessary to the reactivity inthis particular case (Scheme 2a). However, this may be a special casesince the reaction with Et₃SiH proceeded equally well using KOH or NaOHas the catalyst.

The effect of potassium and sodium chelating agents affect silylationwas also explored using a silicon partner that does not perform equallywell with KOH and NaOH. Triethoxysilane was chosen as the test silane,since it only displays product formation using NaOH as the catalyst. Inthis case, the addition of potassium and sodium chelating agents shutdown reactivity, indicating that the sodium ion is indeed necessary forthe silylation of alkynes with triethoxysilane (Scheme 2b). The onlyproduct when crown ethers were added is (EtO)₄Si, which indicates thatsequestration of the alkali metal cation from the system shut down theproductive C—H silylation pathway and induced disproportionation of thesilane. Yields were by GC and NMR analysis.

Example 2.1.4 Comparison of MOH and KOt-Bu Catalysts

In order to compare the performance of the newly-discovered MOH (alkalimetal hydroxide) catalysts with the KOt-Bu catalyst used in the case ofthe heterocyclic silylation, several acetylene substrates and silaneswere subjected to the reaction using KOt-Bu as a catalyst. The resultsare summarized in FIG. 6. Although in the reaction withcyclohexylpropyne and triethylsilane, KOt-Bu successfully produced thesilylated alkyne in moderate yield (as stated in text), in all otherinvestigated cases, KOt-Bu failed to convert the starting material orproduced only trace product. It appears that the acetylinic silylationdescribed herein and the heterocyclic silylation described previouslyrequire different catalysts and might proceed via a distinct mechanism.

Example 3 Experimental and Analytics Example 3.1 General Procedure forCross-Dehydrogenative C(Sp)-H Silylation and Characterization Data

In a nitrogen-filled glove box, catalyst (0.05 mmol, 10 mol %) andalkyne (0.5 mmol, 1 equiv) were added to a 2 dram scintillation vialequipped with a magnetic stirring bar, followed by solvent (0.5 mL) andsilane (1.5 mmol, 3 equiv). The vial was then sealed and the mixture wasstirred at the indicated temperature for the indicated time. The vialwas then removed from the glove box; the reaction mixture was dilutedwith diethyl ether (2 mL), filtered through a short pad of silica gel,and concentrated under reduced pressure. Volatiles were removed underhigh vacuum with heating as indicated and the resultant material waspurified by silica gel flash chromatography if necessary to give thedesired C(sp)-Si product.

(3-Cyclohexylprop-1-yn-1-yl)triethylsilane 2a

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), Et₃SiH (174 mg, 240 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 85° C. for 48 h. The desired product 2a(111.9 mg, 95% yield) was obtained after solvent removal under highvacuum (45 mtorr, 2 hours) as a colorless oil. ¹H NMR (500 MHz, CDCl₃) δ2.13 (d, J=6.6 Hz, 2H), 1.84-1.76 (m, 2H), 1.75-1.68 (m, 2H), 1.65 (dtt,J=12.9, 3.4, 1.5 Hz, 1H), 1.47 (dddd, J=14.8, 6.8, 4.7, 3.4 Hz, 1H),1.24 (tdd, J=15.9, 9.4, 3.4 Hz, 2H), 1.19-1.07 (m, 2H), 1.07-1.01 (m,1H), 0.98 (t, J=7.9 Hz, 9H), 0.57 (q, J=7.9 Hz, 6H); ¹³C NMR (126 MHz,CDCl₃) δ 107.73, 82.39, 37.54, 32.72, 27.86, 26.47, 26.32, 7.65, 4.75.IR (Neat Film NaCl) 3422, 2925, 2172, 1645, 1449, 1018, 802, 724 cm⁻¹;HRMS (EI+) calc'd for C₁₅H₂₇Si [(M+H)—H₂]: 235.1882. found 235.1881.

(3-Cyclohexylprop-1-yn-1-yl)dimethyl(phenyl)silane 2b

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 25° C. for 48 h. The desired product 2b(113.6 mg, 89% yield) was obtained in 95% purity after heating to 85° C.at 45 mtorr for 30 minutes; subsequent purification by silica gel flashchromatography (100% hexanes) yielded the product 2b in analyticallypure form as a colorless oil. R_(f)=0.67 (100% hexanes); ¹H NMR (500MHz, CDCl₃) δ 7.67-7.63 (m, 2H), 7.40-7.34 (m, 3H), 2.19 (d, J=6.6 Hz,2H), 1.87-1.80 (m, 2H), 1.74 (dt, J=12.8, 3.3 Hz, 2H), 1.67 (dddd,J=11.3, 5.2, 3.3, 1.6 Hz, 1H), 1.52 (ddtd, J=14.9, 11.5, 6.7, 3.5 Hz,1H), 1.27 (dddd, J=15.9, 12.6, 9.5, 3.3 Hz, 2H), 1.15 (qt, J=12.7, 3.3Hz, 1H), 1.08-0.98 (m, 2H), 0.41 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ137.93, 133.81, 129.33, 127.91, 108.67, 83.19, 37.42, 32.81, 27.94,26.42, 26.29, −0.38. IR (Neat Film NaCl) 3420, 2924, 2852, 2173, 1646,1448, 1427, 1322, 1248, 1115, 1071, 1027, 815, 730 cm⁻¹; HRMS (EI+)calc'd for C₁₇H₂₅Si [M+H]: 257.1726. found 257.1720.

3-Cyclohexylprop-1-yn-1-yl)(ethyl)dimethylsilane 2c

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), EtMe₂SiH (132 mg, 198 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 24 h. The desired product 2c(95.1 mg, 91% yield) was obtained after solvent removal under highvacuum (45 mtorr, 2 hours) as a colorless oil. ¹H NMR (500 MHz, CDCl₃) δ2.12 (d, J=6.6 Hz, 2H), 1.86-1.76 (m, 2H), 1.77-1.69 (m, 2H), 1.66 (dtd,J=12.6, 3.3, 1.6 Hz, 1H), 1.53-1.40 (m, 1H), 1.32-1.19 (m, 2H),1.20-1.07 (m, 2H), 1.06-0.94 (m, 4H), 0.57 (q, J=7.9 Hz, 2H), 0.12 (s,6H); ¹³C NMR (126 MHz, CDCl₃) δ 107.01, 84.30, 37.46, 32.76, 27.84,26.45, 26.30, 8.47, 7.50, −1.85. IR (Neat Film NaCl) 3422, 2922, 2103,1646, 1558, 1260, 1027, 720 cm⁻¹; HRMS (EI+) calc'd for C₁₃H₂₃Si[(M+H)—H₂]: 207.1569. found 207.1562.

Tributyl(3-cyclohexylprop-1-yn-1-yl)silane 2d

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), n-Bu₃SiH (301 mg, 386 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 2d(117.2 mg, 73% yield) was obtained by silica gel flash chromatography(100% hexanes) yielded the product 2d as a colorless oil. R_(f)=0.78(100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 2.18 (d, J=6.5 Hz, 2H), 1.85(dddd, J=12.3, 6.2, 3.1, 1.8 Hz, 2H), 1.77 (ddd, J=14.0, 4.5, 2.3 Hz,2H), 1.70 (dddt, J=12.8, 5.1, 3.3, 1.5 Hz, 1H), 1.52 (dddt, J=14.5, 7.9,6.6, 3.2 Hz, 1H), 1.43-1.36 (m, 12H), 1.29 (qt, J=12.6, 3.3 Hz, 2H),1.18 (qt, J=12.7, 3.3 Hz, 1H), 1.11-1.02 (m, 2H), 0.97-0.91 (m, 9H),0.67-0.59 (m, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 107.65, 83.25, 37.57,32.72, 27.88, 26.64, 26.46, 26.39, 26.32, 13.98, 13.45. IR (Neat FilmNaCl) 2955, 2922, 2854, 2172, 1449, 1376, 1191, 1080, 1029, 886, 758,708 cm⁻¹; HRMS (EI+) calc'd for C₂₁H₄₀Si [M+•]: 320.2899. found320.2905.

(3-Cyclohexylprop-1-yn-1-yl)diethylsilane 2e

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), Et₂SiH₂ (132 mg, 194 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL oftetrahydrofuran (THF) at 25° C. for 24 h. The desired product 2e (73.6mg, 71% yield) was obtained in 90% purity after solvent removal underhigh vacuum at 45 mtorr for 30 minutes; subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 2e asa colorless oil. R_(f)=0.77 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ3.92 (pt, J=3.2, 1.2 Hz, 1H), 2.15 (dd, J=6.7, 1.2 Hz, 2H), 1.85-1.78(m, 2H), 1.72 (ddd, J=13.9, 4.5, 2.2 Hz, 2H), 1.66 (dddt, J=12.7, 5.1,3.3, 1.5 Hz, 1H), 1.49 (ddtd, J=14.9, 11.5, 6.8, 3.5 Hz, 1H), 1.31-1.20(m, 2H), 1.15 (tt, J=12.6, 3.2 Hz, 1H), 1.07-0.95 (m, 8H), 0.70-0.64 (m,4H); ¹³C NMR (126 MHz, CDCl₃) δ 109.00, 80.24, 37.39, 32.76, 27.91,26.41, 26.28, 8.09, 4.23. IR (Neat Film NaCl) 3422, 2957, 2174, 2120,1646, 1558, 1457, 1260, 1055, 804 cm⁻¹; HRMS (EI+) calc'd for C₁₃H₂₃Si[(M+H)—H₂]: 207.1569. found 207.1562.

Di-tert-butyl(3-cyclohexylprop-1-yn-1-yl)silane 2f

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), t-Bu₂SiH₂ (216 mg, 297 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 2f(120.3 mg, 91% yield) was obtained in 90% purity after high vacuum at 45mtorr for 30 minutes; subsequent purification by silica gel flashchromatography (100% hexanes) yielded the product 2f as a colorless oil.R_(f)=0.88 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 3.57 (t, J=1.2 Hz,1H), 2.17 (dd, J=6.5, 1.2 Hz, 2H), 1.84-1.78 (m, 2H), 1.76-1.70 (m, 2H),1.66 (dddt, J=12.8, 5.1, 3.3, 1.5 Hz, 1H), 1.50 (dddt, J=14.5, 7.8, 6.5,3.1 Hz, 1H), 1.26 (qt, J=12.7, 3.4 Hz, 3H), 1.19-1.09 (m, 2H), 1.06 (s,18H).; ¹³C NMR (126 MHz, CDCl₃) δ 108.94, 79.54, 37.51, 32.75, 28.28,27.88, 26.44, 26.29, 18.63. IR (Neat Film NaCl) 2958, 2927, 2855, 2173,2111, 1469, 1449, 1363, 1028, 1012, 810, 793, 617 cm⁻¹; HRMS (EI+)calc'd for C₁₇H₃₁Si [(M+H)—H₂]: 263.2195. found 263.2206.

Benzyl(3-cyclohexylprop-1-yn-1-yl)dimethylsilane 2g

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), BnMe₂SiH (150 mg, 238 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 2g(101.9 mg, 75% yield) was obtained by silica gel flash chromatography(100% hexanes) as a colorless oil. R_(f)=0.51 (100% hexanes); ¹H NMR(500 MHz, CDCl₃) δ 7.25-7.21 (m, 2H), 7.12-7.08 (m, 3H), 2.20 (s, 2H),2.14 (d, J=6.8 Hz, 2H), 1.81 (ddd, J=13.3, 3.5, 1.5 Hz, 2H), 1.75 (dt,J=12.7, 3.2 Hz, 2H), 1.69 (dddd, J=11.3, 5.3, 3.4, 1.7 Hz, 1H), 1.49(tdt, J=11.4, 6.7, 3.3 Hz, 1H), 1.28 (qt, J=12.6, 3.3 Hz, 2H), 1.16 (qt,J=12.7, 3.3 Hz, 1H), 1.06-0.94 (m, 2H), 0.13 (s, 6H); ¹³C NMR (126 MHz,CDCl₃) δ 139.44, 128.51, 128.19, 124.32, 108.08, 83.69, 37.38, 32.77,27.86, 26.71, 26.41, 26.29, −1.69. IR (Neat Film NaCl) 3081, 3060, 3024,2999, 2922, 2851, 2664, 2173, 1936, 1600, 1493, 1449, 1422, 1408, 1368,1322, 1249, 1207, 1155, 1056, 1029, 947, 839, 761, 697 cm⁻¹; HRMS (EI+)calc'd for C₁₈H₂₆Si [M+•]: 270.1804. found 270.1810.

(3-Cyclohexylprop-1-yn-1-yl)triisopropylsilane 2h

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), i-Pr₃SiH (238 mg, 307 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 85° C. for 48 h. The desired product 2h(95.6 mg, 69% yield) was obtained by silica gel flash chromatography(100% hexanes) as a colorless oil. R_(f)=0.79 (100% hexanes); ¹H NMR(500 MHz, CDCl₃) δ 2.16 (d, J=6.4 Hz, 2H), 1.84-1.77 (m, 2H), 1.73 (dt,J=12.8, 3.4 Hz, 2H), 1.66 (dtd, J=12.7, 3.3, 1.6 Hz, 1H), 1.48 (ddtd,J=14.6, 11.2, 6.5, 3.4 Hz, 1H), 1.25 (qt, J=12.6, 3.4 Hz, 2H), 1.15 (tt,J=12.6, 3.3 Hz, 1H), 1.10-0.99 (m, 23H); ¹³C NMR (126 MHz, CDCl₃) δ108.17, 80.94, 37.64, 32.71, 27.87, 26.49, 26.33, 18.80, 11.48. IR (NeatFilm NaCl) 2924, 2864, 2170, 2463, 1449, 1264, 1025, 995, 883, 743, 676,633 cm⁻¹; HRMS (EI+) calc'd for C₁₈H₃₃Si [(M+H)—H₂]: 277.2352. found277.2349.

(3-Cyclohexylprop-1-yn-1-yl)triethoxysilane 2i

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), (EtO)₃SiH (246 mg, 277 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 2i(97.1 mg, 68% yield) was obtained by silica gel flash chromatography (5%Et₂O in hexanes) as a colorless oil. R_(f)=0.41 (5% Et₂O in hexanes); ¹HNMR (500 MHz, CDCl₃) δ 3.87 (q, J=7.0 Hz, 6H), 2.16 (d, J=6.6 Hz, 2H),1.84-1.78 (m, 2H), 1.72 (dp, J=12.6, 3.7 Hz, 2H), 1.66 (dddt, J=12.8,5.1, 3.3, 1.5 Hz, 1H), 1.52 (ddtd, J=14.9, 11.5, 6.8, 3.5 Hz, 1H), 1.26(t, J=7.0 Hz, 9H), 1.24-1.19 (m, 2H), 1.13 (qt, J=12.7, 3.3 Hz, 1H),1.02 (qd, J=12.7, 3.5 Hz, 2H); ¹³C NMR (126 MHz, CDCl₃) δ 106.50, 76.85,59.02, 37.10, 32.74, 27.55, 26.33, 26.20, 18.18. IR (Neat Film NaCl)2974, 2925, 2852, 2182, 1449, 1390, 1168, 1101, 1079, 1036, 964, 790,721 cm⁻¹; HRMS (EI+) calc'd for C₁₅H₂₉O₃Si [M+H]: 285.1886. found285.1889.

2-((3-Cyclohexylprop-1-yn-1-yl)diisopropylsilyl)pyridine 2j

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), i-Pr₂(Pyr)SiH (290 mg, 322 μL, 1.5 mmol, 3.0 equiv), and 0.5 mLof 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 2j(122.5 mg, 78% yield) was obtained by silica gel flash chromatography(10% EtOAc in hexanes) as a colorless oil. R_(f)=0.47 (10% EtOAc inhexanes); ¹H NMR (500 MHz, THF-d8) δ 8.65 (ddd, J=4.8, 1.7, 1.1 Hz, 1H),7.76 (dt, J=7.5, 1.3 Hz, 1H), 7.59 (td, J=7.6, 1.8 Hz, 1H), 7.19 (ddd,J=7.7, 4.8, 1.4 Hz, 1H), 2.26 (d, J=6.4 Hz, 2H), 1.95-1.84 (m, 2H),1.78-1.73 (m, 2H), 1.67 (dtt, J=13.0, 3.4, 1.6 Hz, 1H), 1.55 (ddtd,J=14.9, 11.4, 6.6, 3.5 Hz, 1H), 1.37-1.26 (m, 4H), 1.21-1.16 (m, 1H),1.16-1.11 (m, 2H), 1.09 (d, J=7.4 Hz, 6H), 0.99 (d, J=7.3 Hz, 6H); ¹³CNMR (126 MHz, THF-d8) δ 164.80, 150.76, 134.42, 132.12, 123.73, 110.50,80.33, 38.63, 33.66, 28.41, 27.38, 27.23, 18.46, 18.40, 12.71. IR (NeatFilm NaCl) 2924, 2862, 2170, 1573, 1462, 1449, 1417, 1136, 1081, 1028,995, 882, 747, 723 cm⁻¹; HRMS (EI+) calc'd for C₂₀H₃₂NSi [M+H]:314.2304. found 314.2311.

2-((3-Cyclohexylprop-1-yn-1-yl)dimethylsilyl)pyridine 2k

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), Me₂(Py)SiH (206 mg, 225 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 2k(99.9 mg, 78% yield) was obtained by silica gel flash chromatography(10% EtOAc in hexanes) as a colorless oil. R_(f)=0.42 (10% EtOAc inhexanes); ¹H NMR (500 MHz, THF-d8) δ 8.65 (ddd, J=4.8, 1.8, 1.1 Hz, 1H),7.74 (dt, J=7.5, 1.2 Hz, 1H), 7.59 (td, J=7.6, 1.8 Hz, 1H), 7.18 (ddd,J=7.7, 4.8, 1.4 Hz, 1H), 2.19 (d, J=6.6 Hz, 2H), 1.88-1.81 (m, 2H),1.73-1.70 (m, 2H), 1.66 (dddd, J=12.7, 5.1, 3.2, 1.5 Hz, 1H), 1.50(dddt, J=14.7, 7.9, 6.7, 3.2 Hz, 1H), 1.28 (tdd, J=16.0, 9.4, 3.4 Hz,2H), 1.17 (qt, J=12.7, 3.3 Hz, 1H), 1.05 (qd, J=12.8, 3.4 Hz, 2H), 0.36(s, 6H); ¹³C NMR (126 MHz, THF-d8) δ 166.55, 150.96, 134.69, 130.13,123.84, 109.23, 83.58, 38.47, 33.68, 28.42, 27.34, 27.22, −1.00. IR(Neat Film NaCl) 3423, 2924, 2852, 2175, 1646, 1449, 1255, 1044, 832,797, 676 cm⁻¹; HRMS (EI+) calc'd for C₁₆H₂₄NSi [M+H]: 258.1678. found258.1672.

1-(3-Cyclohexylprop-1-yn-1-yl)-1,1,2,2,2-pentamethyldisilane 2l

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), Me₅Si₂H (246 mg, 277 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 25° C. for 48 h. The desired product 2l(120.0 mg, 95% yield) was obtained as a cloudy, colorless oil aftersolvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz,THF-d8) δ 2.11 (d, J=6.5 Hz, 2H), 1.81 (dddd, J=13.1, 6.1, 3.1, 1.9 Hz,2H), 1.73-1.69 (m, 2H), 1.65 (dddt, J=12.7, 5.1, 3.2, 1.5 Hz, 1H), 1.44(dddt, J=14.6, 8.0, 6.7, 3.2 Hz, 1H), 1.33-1.21 (m, 2H), 1.15 (qt,J=12.7, 3.2 Hz, 1H), 1.03 (qd, J=12.8, 3.5 Hz, 2H), 0.15 (s, 6H), 0.11(s, 9H); ¹³C NMR (126 MHz, THF-d8) δ 109.11, 84.06, 38.62, 33.61, 28.52,27.37, 27.22, −2.25, −2.35. IR (Neat Film NaCl) 2923, 2852, 2168, 1449,1259, 1244, 1077, 1027, 871, 833, 799, 765, 725, 691, 667 cm⁻¹; HRMS(EI+) calc'd for C₁₄H₂₈Si₂ [M+•]: 252.1730. found 252.1737.

Dimethyl(phenyl)(phenylethynyl)silane 4a

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), ethynylbenzene (52 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 4a(105.7 mg, 89% yield) was obtained in 95% purity after heating to 85° C.at 45 mtorr for 30 minutes; subsequent purification by silica gel flashchromatography (100% hexanes) yielded the product 4a in analyticallypure form as a colorless oil. R_(f)=0.38 (100% hexanes); ¹H NMR (500MHz, THF-d8) δ 7.71-7.65 (m, 2H), 7.49-7.44 (m, 2H), 7.38-7.28 (m, 6H),0.46 (s, 6H). ¹³C NMR (126 MHz, THF-d8) δ 137.86, 134.66, 132.88,130.35, 129.75, 129.28, 128.79, 124.15, 107.86, 92.55, −0.50. IR (NeatFilm NaCl) 3068, 3051, 2959, 2899, 2158, 1592, 1488, 1442, 1428, 1278,1250, 1219, 1118, 1068, 1026, 846, 807, 780, 731, 690 cm⁻¹; HRMS (EI+)calc'd for C₁₆H₁₇Si [M+H]: 237.1100. found 237.1101.

((4-Fluorophenyl)ethynyl)dimethyl(phenyl)silanepyridine 4b

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-ethynyl-4-fluorobenzene (60 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4b (111.9 mg, 88% yield) was obtained in 95% purity aftersolvent removal at 85° C. at 45 mtorr for 30 minutes; subsequentpurification by silica gel flash chromatography (100% hexanes) yieldedthe product 4b in analytically pure form as a colorless oil. R_(f)=0.49(100% hexanes); ¹H NMR (500 MHz, THF-d8) δ 7.68-7.65 (m, 2H), 7.53-7.48(m, 2H), 7.34 (dd, J=4.9, 1.9 Hz, 3H), 7.08 (t, J=8.8 Hz, 2H), 0.46 (s,6H); ¹³C NMR (126 MHz, THF-d8) δ 163.93 (d, J=248.7 Hz), 137.74, 135.10(d, J=8.5 Hz), 134.65, 130.39, 128.81, 120.43 (d, J=3.5 Hz), 116.51 (d,J=22.4 Hz), 106.68, 92.43 (d, J=1.3 Hz), −0.56. IR (Neat Film NaCl)3420, 3069, 2961, 2160, 1653, 1600, 1505, 1428, 1251, 1233, 1155, 1117,1092, 857, 835, 816, 781, 731, 698 cm⁻¹; HRMS (EI+) calc'd for C₁₆H₁₆FSi[M+H]: 255.1005. found 255.1000.

((4-Bromophenyl)ethynyl)dimethyl(phenyl)silane 4c

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-bromo-4-ethynylbenzene (90 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4c (81.3 mg, 52% yield) was obtained in 80% purity after solventremoval at 85° C. at 45 mtorr for 30 minutes; subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 4c ascolourless crystals in a 9:1 mixture with diphenyltetramethyldisiloxane.R_(f)=0.54 (100% hexanes); ¹H NMR (500 MHz, THF-d8) δ 7.69-7.63 (m, 2H),7.51 (d, J=8.5 Hz, 2H), 7.39 (d, J=8.5 Hz, 2H), 7.36-7.30 (m, 3H), 0.46(s, 6H); ¹³C NMR (126 MHz, THF-d8) δ 137.55, 134.65, 134.53, 132.66,130.44, 128.83, 123.94, 123.19, 106.51, 94.19, −0.66. IR (Neat FilmNaCl) 3068, 2958, 2159, 1653, 1540, 1484, 1473, 1457, 1427, 1249, 1214,1114, 1071, 1010, 846, 830, 780, 730, 698 cm⁻¹; HRMS (EI+) calc'd forC₁₆H₁₆Si¹⁸Br [M+H]: 317.0184. found 317.0180.

((3-Chlorophenyl)ethynyl)dimethyl(phenyl)silane 4d

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-chloro-3-ethynylbenzene (68 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 45° C. for 24 h. The desiredproduct 4d (121.6 mg, 90% yield) was obtained in 95% purity aftersolvent removal at 85° C. at 45 mtorr for 30 minutes; subsequentpurification by silica gel flash chromatography (100% hexanes) yieldedthe product 4d in analytically pure form as a colorless oil. R_(f)=0.42(100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.70-7.66 (m, 2H), 7.49 (ddd,J=2.1, 1.5, 0.5 Hz, 1H), 7.40 (dd, J=5.0, 1.9 Hz, 3H), 7.38 (dt, J=7.6,1.4 Hz, 1H), 7.31 (ddd, J=8.1, 2.1, 1.2 Hz, 1H), 7.24 (ddd, J=8.0, 7.6,0.5 Hz, 1H), 0.51 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 136.75, 134.21,133.86, 132.05, 130.29, 129.70, 129.61, 129.12, 128.10, 124.77, 105.13,93.82, −0.79. IR (Neat Film NaCl) 3420, 2163, 1684, 1647, 1559, 1521,1507, 1457, 1249, 1117, 1091, 884, 781, 681 cm⁻¹; HRMS (EI+) calc'd forC₁₆H₁₆ClSi [M+H]: 271.0710. found 271.0710.

4-((Dimethyl(phenyl)silyl)ethynyl)-N,N-dimethylaniline 4e

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 4-ethynyl-N,N-dimethylaniline (73 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4e (139.4 mg, 100% yield) was obtained as colourless crystalsafter solvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500MHz, CDCl₃) δ 7.73-7.68 (m, 2H), 7.41-7.36 (m, 5H), 6.61 (d, J=8.9 Hz,2H), 2.98 (s, 6H), 0.48 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 150.46,137.88, 133.93, 133.38, 129.36, 127.94, 111.69, 109.78, 108.49, 89.19,40.32, −0.39. IR (Neat Film NaCl) 3067, 2957, 2147, 1682, 1607, 1519,1487, 1427, 1360, 1248, 1186, 1115, 945, 850, 817, 779, 730, 699, 653cm⁻¹; HRMS (EI+) calc'd for C₁₈H₂₁NSi [M+•]: 279.1443. found 279.1445.

Dimethyl(phenyl)(p-tolylethynyl)silane 4f

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-ethynyl-4-methylbenzene (58 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4f (115.5 mg, 92% yield) was obtained as a pale yellow oil aftersolvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz,CDCl₃) δ 7.71 (ddt, J=6.0, 2.4, 1.1 Hz, 2H), 7.41 (ddq, J=5.8, 3.0, 0.9Hz, 5H), 7.16-7.10 (m, 2H), 2.37 (s, 3H), 0.51 (d, J=1.1 Hz, 6H); ¹³CNMR (126 MHz, CDCl₃) δ 139.02, 137.33, 133.90, 132.10, 129.52, 129.12,128.02, 120.00, 107.18, 91.28, 21.69, −0.59. IR (Neat Film NaCl) 3420,3068, 3049, 2959, 2920, 2156, 1507, 1428, 1408, 1249, 1223, 1117, 1020,851, 816, 780, 731, 700, 656 cm⁻¹; HRMS (EI+) calc'd for C₁₇H₁₉Si [M+H]:251.1256. found 251.1257.

((4-Methoxyphenyl)ethynyl)dimethyl(phenyl)silane 4g

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-ethynyl-4-methoxybenzene (66 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4g (121.6 mg, 91% yield) was obtained in 95% purity aftersolvent removal at 85° C. at 45 mtorr for 30 minutes; subsequentpurification by silica gel flash chromatography (100% hexanes→5% EtOAcin hexanes) yielded the product 4g in analytically pure form as a yellowoil. R_(f)=0.27 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.71 (dd,J=6.5, 3.0 Hz, 2H), 7.46 (d, J=8.9 Hz, 2H), 7.43-7.38 (m, 3H), 6.84 (d,J=8.9 Hz, 2H), 3.82 (s, 3H), 0.51 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ160.02, 137.42, 133.89, 133.73, 129.50, 128.01, 115.20, 113.96, 107.03,90.47, 55.42, −0.56. IR (Neat Film NaCl) 3068, 2959, 2154, 1605, 1507,1441, 1293, 1249, 1171, 1116, 1032, 853, 832, 812, 779, 755, 731, 699cm⁻¹; HRMS (EI+) calc'd for C₁₇H₁₈OSi [M+•]: 266.1127. found 266.1135.

((3,5-Dimethoxyphenyl)ethynyl)dimethyl(phenyl)silane 4h

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-ethynyl-3,5-dimethoxybenzene (81 mg,0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv),and 0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4h (140.6 mg, 95% yield) was obtained as a light yellow oilafter solvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500MHz, CDCl₃) δ 7.70 (ddd, J=5.5, 2.7, 1.2 Hz, 2H), 7.41 (dd, J=4.6, 2.1Hz, 3H), 6.67 (d, J=2.3 Hz, 2H), 6.47 (t, J=2.3 Hz, 1H), 3.79 (s, 6H),0.52 (d, J=1.5 Hz, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 160.56, 137.05,133.90, 129.61, 128.05, 124.29, 109.87, 106.78, 102.53, 91.75, 55.57,−0.68. IR (Neat Film NaCl) 3421, 3069, 3001, 2959, 2837, 2160, 1596,1456, 1419, 1348, 1298, 1250, 1205, 1155, 1116, 1064, 979, 964, 817,753, 732, 681 cm⁻¹; HRMS (EI+) calc'd for C₁₈H₂₁O₂Si [M+H]: 297.1311.found 297.1309.

2-Ethynyl-1,3,5-trimethylbenzene 4i

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 2-ethynyl-1,3,5-trimethylbenzene (57 mg,0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv),and 0.5 mL of 1,2-dimethoxyethane (DME) at 25° C. for 24 h. The desiredproduct 4i (119.1 mg, 86% yield) was obtained as a colorless oil aftersolvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz,CDCl₃) δ 7.73 (ddt, J=4.5, 3.2, 0.8 Hz, 3H), 7.40 (dd, J=2.5, 0.8 Hz,2H), 6.88-6.86 (m, 2H), 2.42 (s, 6H), 2.29 (s, 3H), 0.52 (t, J=0.7 Hz,6H); ¹³C NMR (126 MHz, CDCl₃) δ 140.86, 138.23, 137.66, 133.89, 129.45,127.99, 127.67, 119.94, 104.95, 99.66, 21.51, 21.15, −0.34. IR (NeatFilm NaCl) 3440, 3068, 2959, 2146, 1646, 1610, 1474, 1428, 1224, 1117,841, 825, 779, 753, 698 cm⁻¹; HRMS (EI+) calc'd for C₁₉H₂₃Si [M+H]:279.1569. found 279.1561.

((6-Methoxynaphthalen-2-yl)ethynyl)dimethyl(phenyl)silane 4j

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 2-ethynyl-6-methoxynaphthalene (91 mg,0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv),and 0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4j (134.8 mg, 85% yield) was obtained in 95% purity as acolorless oil after solvent removal at 85° C. at 45 mtorr for 30minutes. This product decomposes on silica. ¹H NMR (500 MHz, CDCl₃) δ7.99 (dd, J=1.5, 0.7 Hz, 1H), 7.78-7.72 (m, 2H), 7.70 (d, J=9.0 Hz, 1H),7.68 (d, J=8.2 Hz, 1H), 7.53 (dd, J=8.4, 1.6 Hz, 1H), 7.46-7.40 (m, 3H),7.17 (dd, J=8.9, 2.5 Hz, 1H), 7.11 (d, J=2.6 Hz, 1H), 3.93 (s, 3H), 0.56(s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 158.57, 137.30, 134.48, 133.93,132.17, 129.56, 129.34, 128.44, 128.05, 126.85, 122.76, 119.59, 117.93,107.50, 105.91, 91.68, 55.50, −0.57. IR (Neat Film NaCl) 3422, 2959,2152, 1631, 1601, 1499, 1481, 1461, 1390, 1267, 1232, 1161, 1117, 1031,937, 890, 814, 780, 731, 703, 656 cm⁻¹; HRMS (EI+) calc'd for C₂₁H₂₀OSi[M+•]: 316.1284. found 316.1296.

5-((Dimethyl(phenyl)silyl)ethynyl)-1-methyl-1H-imidazole 4k

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 5-ethynyl-1-methyl-1H-imidazole (53 mg,0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv),and 0.5 mL of 1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desiredproduct 4k (98.7 mg, 82% yield) was obtained in 95% purity after solventremoval at 85° C. at 45 mtorr for 30 minutes; subsequent purification bysilica gel flash chromatography (100% EtOAc) yielded the product 4k inanalytically pure form as a colorless oil. R_(f)=0.45 (100% EtOAc); ¹HNMR (500 MHz, CDCl₃) δ 7.68-7.65 (m, 2H), 7.40 (m, 4H), 7.31 (d, J=1.0Hz, 1H), 3.68-3.65 (m, 3H), 0.52 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ138.37, 136.49, 135.29, 133.74, 129.73, 128.09, 116.28, 100.60, 94.11,32.11, −0.85. IR (Neat Film NaCl) 3417, 2960, 2157, 1646, 1533, 1489,1428, 1274, 1250, 1227, 1116, 924, 823, 782, 732, 702, 661 cm⁻¹; HRMS(EI+) calc'd for C₁₄H₁₇N₂Si [M+H]: 241.1161. found 241.1169.

Dimethyl(phenyl)(thiophen-3-ylethynyl)silane 4l

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 3-ethynylthiophene (54 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 60 h. The desired product 4l(113.2 mg, 93% yield) was obtained in 95% purity after solvent removalat 85° C. at 45 mtorr for 30 minutes; subsequent purification by silicagel flash chromatography (100% hexanes) yielded the product 4l inanalytically pure form as a colorless oil. R_(f)=0.39 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.72-7.68 (m, 2H), 7.53 (dd, J=3.0, 1.2 Hz, 1H),7.43-7.39 (m, 3H), 7.27-7.24 (m, 1H), 7.17 (dd, J=5.0, 1.2 Hz, 1H), 0.51(s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 137.08, 133.88, 130.26, 130.11,129.59, 128.04, 125.36, 122.32, 101.67, 91.93, −0.68. IR (Neat FilmNaCl) 3107, 3068, 2959, 2152, 1427, 1356, 1249, 1163, 1116, 944, 870,781, 753, 698 cm⁻¹; HRMS (EI+) calc'd for C₁₄H₁₄SSi [M+•]: 242.0586.found 242.0576.

3-((Dimethyl(phenyl)silyl)ethynyl)pyridine 4m

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 3-ethynylpyridine (52 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 4m(91.8 mg, 77% yield) was obtained in 95% purity after solvent removal at85° C. at 45 mtorr for 30 minutes; subsequent purification by silica gelflash chromatography (100% hexanes) yielded the product 4m inanalytically pure form as a colorless oil. R_(f)=0.31 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 8.74 (dd, J=2.1, 0.9 Hz, 1H), 8.54 (dd, J=4.9,1.7 Hz, 1H), 7.77 (ddd, J=7.9, 2.1, 1.7 Hz, 1H), 7.71-7.67 (m, 2H), 7.42(dd, J=4.9, 1.9 Hz, 3H), 7.24 (ddd, J=7.9, 4.9, 0.9 Hz, 1H), 0.54 (s,6H); ¹³C NMR (126 MHz, CDCl₃) δ 152.82, 149.02, 139.01, 136.49, 133.81,129.74, 128.11, 123.00, 120.21, 103.14, 96.34, −0.88. IR (Neat FilmNaCl) 3420, 3069, 3048, 3025, 2960, 2161, 1559, 1474, 1406, 1250, 1184,1119, 1022, 847, 781, 754, 703, 670 cm⁻¹; HRMS (EI+) calc'd forC₁₅H₁₆NSi [M+H]: 238.1052. found 238.1049.

((Dimethyl(phenyl)silyl)ethynyl)ferrocene 4n

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), ethynylferrocene (105 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4n(170.1 mg, 99% yield) was obtained as a red crystalline solid aftersolvent removal at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz,CDCl₃) δ 7.70 (dd, J=6.1, 3.1 Hz, 2H), 7.43-7.37 (m, 3H), 4.48 (s, 2H),4.21 (m, 7H), 0.47 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 137.71, 133.89,129.44, 127.98, 106.30, 88.52, 72.02, 70.26, 69.00, 64.64, −0.40. IR(Neat Film NaCl) 2958, 2147, 1428, 1248, 1106, 1024, 1001, 925, 819,779, 753, 730, 699 cm⁻¹; HRMS (EI+) calc'd for C₂₀H₂₀FeSi [M+•]:344.0684. found 344.0696.

(Cyclohex-1-en-1-ylethynyl)dimethyl(phenyl)silane 4o

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 1-ethynylcyclohex-1-ene (53 mg, 0.5 mmol,1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mLof 1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4o(102.7 mg, 85% yield) was obtained in 95% purity after solvent removalat 85° C. at 45 mtorr for 15 minutes; subsequent purification by silicagel flash chromatography (100% hexanes) yielded the product 4o inanalytically pure form as a colorless oil. R_(f)=0.50 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.67-7.63 (m, 2H), 7.39-7.36 (m, 3H), 6.24 (tt,J=3.9, 1.8 Hz, 1H), 2.17 (tdd, J=6.0, 2.7, 1.8 Hz, 2H), 2.11 (tdd,J=6.4, 4.6, 2.5 Hz, 2H), 1.68-1.55 (m, 4H), 0.43 (s, 6H); ¹³C NMR (126MHz, CDCl₃) δ 137.59, 136.90, 133.84, 129.40, 127.94, 120.82, 109.17,88.79, 29.14, 25.81, 22.33, 21.54, −0.51. IR (Neat Film NaCl) 3422,2937, 2145, 1647, 1428, 1249, 1116, 863, 819, 779, 730, 698 cm⁻¹; HRMS(EI+) calc'd for C₁₆H₂₁Si [M+H]: 241.1413. found 241.1402.

(Cyclohexylethynyl)dimethyl(phenyl)silane 4p

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), ethynylcyclohexane (54 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 25° C. for 48 h. The desired product 4p(97.4 mg, 80% yield) was obtained in 80% purity after solvent removal at85° C. at 45 mtorr for 15 minutes; subsequent purification by silica gelflash chromatography (100% hexanes) yielded the product 4p as acolorless oil in a 9:1 mixture with diphenyltetramethyldisiloxane.R_(f)=0.53 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.65 (ddd, J=5.4,2.4, 1.7 Hz, 2H), 7.37 (ddq, J=4.0, 1.9, 0.8 Hz, 3H), 2.47 (tt, J=9.0,3.8 Hz, 1H), 1.89-1.79 (m, 2H), 1.73 (ddd, J=9.8, 6.2, 3.1 Hz, 2H), 1.52(td, J=9.7, 9.2, 3.8 Hz, 3H), 1.38-1.26 (m, 3H), 0.40 (d, J=1.0 Hz, 6H);¹³C NMR (126 MHz, CDCl₃) δ 133.82, 133.13, 129.29, 127.89, 113.93,81.74, 32.70, 30.23, 26.00, 24.93, −0.30. IR (Neat Film NaCl) 2931,2854, 2173, 1448, 1427, 1248, 1116, 1076, 843, 834, 816, 779, 729, 698cm⁻¹¹; HRMS (EI+) calc'd for C₁₆H₂₁Si [(M+H)—H₂]: 241.1413. found241.1419.

(3-Methoxyprop-1-yn-1-yl)dimethyl(phenyl)silane 4q

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 3-methoxyprop-1-yne (35 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4q(61.0 mg, 60% yield) was obtained in 95% purity after solvent removal at85° C. at 45 mtorr for 15 minutes; careful heating is necessary, as theproduct is volatile under these conditions. Subsequent purification bysilica gel flash chromatography (1:1 DCM:hexanes) yielded the product 4qin analytically pure form as a colorless oil. R_(f)=0.38 (1:1DCM:hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.65-7.62 (m, 2H), 7.41-7.36 (m,3H), 4.16 (s, 2H), 3.41 (s, 3H), 0.45 (s, 6H); ¹³C NMR (126 MHz, CDCl₃)δ 136.63, 133.66, 129.49, 127.90, 103.05, 89.53, 60.48, 57.67, −0.97. IR(Neat Film NaCl) 3423, 2925, 2173, 1640, 1428, 1353, 1250, 1186, 1103,1007, 990, 903, 838, 817, 781, 731, 698 cm⁻¹; HRMS (EI+) calc'd forC₁₂H₁₆OSi [M+•]: 204.0971. found 204.0977.

(Cyclopropylethynyl)dimethyl(phenyl)silane 4r

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), ethynylcyclopropane (33 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 25° C. for 48 h. The desired product 4r(70.1 mg, 70% yield) was obtained in 95% purity after solvent removal at85° C. at 45 mtorr for 30 minutes; careful heating is necessary, as thisproduct is volatile under these conditions. Subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 4r inanalytically pure form as a colorless oil. R_(f)=0.38 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.64-7.61 (m, 2H), 7.39-7.36 (m, 3H), 1.40-1.30(m, 1H), 0.87-0.75 (m, 4H), 0.40 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ137.77, 133.79, 129.36, 127.92, 112.40, 77.65, 8.97, 0.70, −0.45. IR(Neat Film NaCl) 3423, 3068, 2960, 2172, 2158, 1646, 1428, 1348, 1249,1114, 1028, 839, 779, 730, 659 cm⁻¹; HRMS (EI+) calc'd for C₁₃H₁₆Si[M+•]: 200.1021. found 200.1031.

Dimethyl(oct-1-yn-1-yl)(phenyl)silane 4s

The general procedure was followed.

The reaction was performed with NaOH (2.0 mg, 0.05 mmol, 10 mol %),oct-1-yne (55 mg, 0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5mmol, 3.0 equiv), and 0.5 mL of 1,2-dimethoxyethane (DME) at 25° C. for48 h. The desired product 4s (101.0 mg, 83% yield) was obtained in 95%purity after solvent removal at 85° C. at 45 mtorr for 15 minutes;subsequent purification by silica gel flash chromatography (100%hexanes) yielded the product 4s in analytically pure form as a colorlessoil. R_(f)=0.53 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.67-7.62 (m,2H), 7.40-7.35 (m, 3H), 2.28 (t, J=7.1 Hz, 2H), 1.59-1.53 (m, 2H),1.47-1.39 (m, 2H), 1.35-1.27 (m, 4H), 0.91 (t, J=6.9 Hz, 3H), 0.40 (s,6H); ¹³C NMR (126 MHz, CDCl₃) δ 137.86, 133.80, 129.35, 127.92, 109.85,82.31, 31.43, 28.68, 28.64, 22.69, 20.12, 14.19, −0.44. IR (Neat FilmNaCl) 3422, 3069, 2957, 2931, 2858, 2174, 1647, 1428, 1248, 1115, 836,815, 779, 729, 699 cm⁻¹; HRMS (EI+) calc'd for C₁₆H₂₃Si [M+H]: 245.1726.found 245.1727.

Dimethyl(phenyl)(4-phenylbut-1-yn-1-yl)silane 4t

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), but-3-yn-1-ylbenzene (65 mg, 0.5 mmol,1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mLof 1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4t(130.0 mg, 98% yield) was obtained as a pale yellow oil after solventremoval at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz, CDCl₃) δ7.64-7.59 (m, 2H), 7.42-7.37 (m, 3H), 7.31 (dd, J=8.0, 6.8 Hz, 2H),7.28-7.23 (m, 3H), 2.90 (t, J=7.5 Hz, 2H), 2.60 (t, J=7.5 Hz, 2H), 0.42(d, J=0.6 Hz, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 140.63, 137.56, 133.80,129.39, 128.68, 128.47, 127.93, 126.43, 108.62, 83.39, 35.10, 22.38,−0.56. IR (Neat Film NaCl) 3423, 3086, 3067, 3027, 2959, 2174, 1647,1602, 1495, 1453, 1427, 1248, 1114, 1077, 1042, 869, 811, 779, 729, 696,661 cm⁻¹; HRMS (EI+) calc'd for C₁₈H₁₉Si [(M+H)—H₂]: 263.1256. found263.1258.

Deca-1,5-diyn-1-yldimethyl(phenyl)silane 4u

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), deca-1,5-diyne (67 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4u(131.3 mg, 98% yield) was obtained as a colorless oil after solventremoval at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz, CDCl₃) δ7.68-7.64 (m, 2H), 7.38 (dd, J=5.0, 1.9 Hz, 3H), 2.49 (ddd, J=7.7, 6.1,1.7 Hz, 2H), 2.46-2.39 (m, 2H), 2.18 (tt, J=7.0, 2.3 Hz, 2H), 1.52-1.39(m, 4H), 0.92 (t, J=7.2 Hz, 3H), 0.42 (s, 6H); ¹³C NMR (126 MHz, CDCl₃)δ 137.56, 133.81, 129.40, 127.92, 107.79, 83.33, 81.59, 78.33, 31.20,22.05, 20.79, 19.16, 18.54, 13.77, −0.54. IR (Neat Film NaCl) 2958,2932, 2872, 2177, 1465, 1428, 1336, 1249, 1115, 1042, 870, 837, 816,780, 754, 731, 700, 662 cm⁻¹; HRMS (EI+) calc'd for C₁₈H₂₃Si [(M+H)—H₂]:267.1569. found 267.1565.

(5-Chloropent-1-yn-1-yl)dimethyl(phenyl)silane 4v

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), 5-chloropent-1-yne (51 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 4v(93.3 mg, 79% yield) was obtained in 95% purity after solvent removal at85° C. at 45 mtorr for 30 minutes; careful heating is necessary, as thisproduct is volatile under these conditions. Subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 4v inanalytically pure form as a colorless oil. R_(f)=0.31 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.65-7.60 (m, 2H), 7.38 (dd, J=4.9, 1.9 Hz, 3H),3.67 (t, J=6.4 Hz, 2H), 2.49 (t, J=6.8 Hz, 2H), 2.01 (p, J=6.6 Hz, 2H),0.41 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 137.46, 133.75, 129.48, 127.99,107.20, 83.81, 43.77, 31.40, 17.57, −0.56. IR (Neat Film NaCl) 3420,3069, 2960, 2928, 2174, 1646, 1428, 1249, 1114, 1041, 837, 816, 780,731, 701, 665 cm⁻¹; HRMS (EI+) calc'd for C₁₃H₁₆ClSi [(M+H)—H₂]:235.0710. found 235.0713.

3-(Dimethyl(phenyl)silyl)-N-methylprop-2-yn-1-amine 4w

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), N-methylprop-2-yn-1-amine (69 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desiredproduct 4w (81.8 mg, 80% yield) was obtained in 95% purity after solventremoval at 85° C. at 45 mtorr for 15 minutes; careful heating isnecessary, as the product is volatile under these conditions. Subsequentpurification by silica gel flash chromatography (100% EtOAc) yielded theproduct 4w in analytically pure form as a colorless oil. R_(f)=0.32(100% EtOAc); ¹H NMR (500 MHz, THF-d8) δ 7.63-7.59 (m, 2H), 7.33-7.29(m, 3H), 3.36 (s, 2H), 2.39 (s, 3H), 0.36 (s, 6H); ¹³C NMR (126 MHz,THF-d8) δ 138.26, 134.58, 130.18, 128.67, 108.45, 85.45, 41.75, 35.64,−0.33. IR (Neat Film NaCl) 3416, 3068, 2957, 2165, 1725, 1651, 1427,1250, 1116, 1044, 836, 817, 730, 699 cm⁻¹; HRMS (EI+) calc'd forC₁₂H₁₈NSi [M+H]: 204.1208. found 204.1214.

(3-((Dimethyl(phenyl)silyl)oxy)prop-1-yn-1-yl)dimethyl(phenyl)silane 4x

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), prop-2-yn-1-ol (28 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 24 h. The desired product 4x(142.9 mg, 88% yield) was obtained as a colorless oil after solventremoval at 85° C. at 45 mtorr for 30 minutes. Careful heating isnecessary, as the product is volatile under these conditions. ¹H NMR(500 MHz, CDCl₃) δ 7.62 (ddt, J=6.4, 1.8, 0.9 Hz, 4H), 7.44-7.36 (m,6H), 4.35 (s, 2H), 0.48 (s, 6H), 0.43 (s, 6H); ¹³C NMR (126 MHz, CDCl₃)δ 137.08, 136.80, 133.82, 133.73, 129.93, 129.57, 128.01, 127.98,105.77, 88.23, 52.27, −0.93, −1.36. IR (Neat Film NaCl) 3069, 3049,2959, 2177, 1428, 1363, 1250, 1117, 1085, 1043, 1004, 817, 782, 731, 698cm⁻¹; HRMS (EI+) calc'd for C₁₉H₂₃OSi₂ [(M+H)—H₂]: 323.1288. found323.1297.

5-(Prop-2-yn-1-yl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 3y

To a mixture of tetrahydrothieno[3,2-c]pyridine hydrochloride (1.40 g,10 mmol, 1 equiv) and K₂CO₃ (2.76 g, 20 mmol, 2 equiv) in DMF (30 ml),was added 1-propyne-3-bromide (1.18 g, 10 mmol, 1 equiv) and the mixturewas stirred at room temperature for 16 h. The mixture was filtered andsolvent was removed under reduced pressure to give a brown oil. This oilwas diluted with 20 mL of diethyl ether and washed with 20 mL of water,then 20 mL brine, then dried over anhydrous Na₂SO₄. The solvent wasremoved in vacuo and the residue was purified by column chromatographyon silica gel (10:1 hexanes:Et₂O) yielding the product 3y as a yellowliquid (1.27 g, 72% yield). R_(f)=0.35 (10% EtOAc in hexanes); ¹H NMR(500 MHz, CDCl₃) δ 7.08 (dt, J=5.1, 0.7 Hz, 1H), 6.73 (d, J=5.1 Hz, 1H),3.69 (t, J=1.7 Hz, 2H), 3.53 (d, J=2.4 Hz, 2H), 2.95-2.91 (m, 2H),2.91-2.88 (m, 2H), 2.29 (t, J=2.4 Hz, 1H); ¹³C NMR (126 MHz, CDCl₃) δ133.55, 132.89, 125.19, 122.83, 78.78, 73.39, 51.50, 49.70, 46.37,25.57. IR (Neat Film NaCl) 3937, 3626, 3390, 3289, 3103, 3065, 2910,2816, 2101, 2651, 1614, 1565, 1461, 1428, 1405, 1328, 1275, 1219, 1191,1166, 1130, 1109, 1079, 1051, 1017, 983, 902, 835, 789, 703 cm⁻¹; HRMS(EI+) calc'd for C₁₀H₁₂NS [M+H]: 178.0690. found 178.0689.

5-(3-(Dimethyl(phenyl)silyl)prop-2-yn-1-yl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine4y

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %),5-(prop-2-yn-1-yl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (89 mg, 0.5mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and0.5 mL of 1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desiredproduct 4y (120.4 mg, 77% yield) was obtained in 95% purity aftersolvent removal at 85° C. at 45 mtorr for 15 minutes; subsequentpurification by silica gel flash chromatography (10% EtOAc in hexanes)yielded the product 4y in analytically pure form as a yellow oil.R_(f)=0.40 (10% EtOAc in hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.67-7.61(m, 2H), 7.43-7.34 (m, 3H), 7.09 (dd, J=5.1, 0.8 Hz, 1H), 6.75 (d, J=5.1Hz, 1H), 3.72 (t, J=1.6 Hz, 2H), 3.61 (d, J=0.7 Hz, 2H), 2.99-2.88 (m,4H), 0.43 (s, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 137.12, 133.78, 133.16,133.06, 129.54, 128.00, 125.36, 122.92, 102.74, 88.35, 51.69, 49.89,47.60, 25.69, −0.60. IR (Neat Film NaCl) 3067, 2957, 2906, 2814, 2163,1427, 1327, 1249, 1166, 1115, 1034, 1016, 975, 836, 817, 780, 731, 699cm⁻¹; HRMS (EI+) calc'd for C₁₈H₂₀NSSi [(M+H)—H₂]: 310.1086. found310.1087.

Example 3.2 Procedure for the Multi-Gram Scale Synthesis of 4s

Dimethyl(oct-1-yn-1-yl)(phenyl)silane 4s

A 500 mL oven-dried Schlenk flask equipped with a stir bar and stopperedwith a rubber septum was evacuated and refilled once with argon. NaOH(364 mg, 9.1 mmols, 10 mol %) was weighed out on the bench and added tothe flask under a strong flow of argon. The charged flask was thenevacuated and heated under vacuum for 2 minutes with a heat gun, thenrefilled with argon. 1,2-dimethoxyethane (DME) (degassed, 90 mL),1-octyne (13.4 mL, 90.7 mmol, 1.0 equiv) and PhMe₂SiH (20.9 mL, 136.1mmol, 1.5 equiv) were added through the septum by syringe. The flask wasthen heated with a heating mantle set at 45° C. and stirred for 60hours. The flask with the resultant cloudy brown-tan solution wasremoved from heating and allowed to cool to room temperature, dilutedwith anhydrous Et₂O (50 mL), and filtered through a short pad of silicato remove solid residue. After the solvent was removed in vacuo, astirbar was added and the transparent deep amber solution was stirredunder high vacuum (100 millitorr) for several hours to remove remainingvolatiles. The mixture was then subjected to distillation under vacuum:

-   -   a) Heating bath to 80 OC, vacuum stabilizes at 200 millitorr as        a small amount of droplets condense into the forerun. Forerun        comes off as a colorless liquid. Thermometer reads 22° C.    -   b) Vacuum stays at 200 millitorr. Heating bath set to 85° C. as        the last of the remaining silane boils off.    -   c) Heating bath temperature increased to 125° C. The solution        starts to boil slowly. Thermometer reads 60° C. Vacuum stays at        200 millitorr.    -   d) Increase temperature to 130° C., vacuum at 200 millitorr to        distill over the desired dimethyl(oct-1-yn-1-yl)(phenyl)silane        (colorless oil). Thermometer reads 85° C. The desired product 4s        is obtained as a colorless oil (19.0 g, 86% yield).

Example 3.3 Synthesis of mono- and bis-silylated diynes

Deca-1,9-diyn-1-yldimethyl(phenyl)silane 5a

The general procedure was followed. The reaction was performed with KOH(5.6 mg, 0.1 mmol, 20 mol %), deca-1,9-diyne (67 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 24 h. The desired product 5a(126.2 mg, 94% yield) was obtained in 95% purity after solvent removalat 85° C. at 45 mtorr for 20 minutes; subsequent purification by silicagel flash chromatography (100% hexanes) yielded the product 5a inanalytically pure form as a colorless oil. R_(f)=0.48 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.66-7.61 (m, 2H), 7.40-7.35 (m, 3H), 2.29 (t,J=7.1 Hz, 2H), 2.20 (td, J=7.1, 2.6 Hz, 2H), 1.96 (t, J=2.6 Hz, 1H),1.57 (dtd, J=9.6, 7.1, 4.5 Hz, 4H), 1.47-1.42 (m, 4H), 0.40 (s, 6H); ¹³CNMR (126 MHz, CDCl₃) δ 137.79, 133.78, 129.37, 127.93, 109.55, 84.74,82.51, 68.34, 28.51, 28.45, 28.39, 28.31, 20.04, 18.48, −0.46. IR (NeatFilm NaCl) 3420, 3306, 3068, 2936, 2859, 2173, 2117, 1646, 1457, 1428,1325, 1248, 1114, 1026, 836, 816, 754, 731, 700, 661 cm⁻¹; HRMS (EI+)calc'd for C₁₈H₂₃Si [(M+H)—H₂]: 267.1569. found 267.1556.

1,10-Bis(dimethyl(phenyl)silyl)deca-1,9-diyne 5b

The general procedure was followed. The reaction was performed with KOH(5.6 mg, 0.1 mmol, 20 mol %), deca-1,9-diyne (67 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 5b(190.9 mg, 95% yield) was obtained in 95% purity after solvent removalat 85° C. at 45 mtorr for 30 minutes; subsequent purification by silicagel flash chromatography (100% hexanes) yielded the product 5b inanalytically pure form as a colorless oil. R_(f)=0.43 (100% hexanes); ¹HNMR (500 MHz, CDCl₃) δ 7.65 (ddt, J=5.4, 3.0, 1.4 Hz, 4H), 7.38 (ddt,J=4.4, 2.2, 1.1 Hz, 6H), 2.30 (td, J=7.2, 1.1 Hz, 4H), 1.59 (t, J=6.8Hz, 4H), 1.49-1.42 (m, 4H), 0.43-0.40 (s, 12H); ¹³C NMR (126 MHz, CDCl₃)δ 137.79, 133.78, 129.37, 127.93, 109.58, 82.49, 28.53, 28.38, 20.04,−0.45. IR (Neat Film NaCl) 3423, 3068, 2937, 2858, 2173, 1647, 1428,1248, 1114, 836, 815, 753, 730, 699, 661 cm⁻¹; HRMS (EI+) calc'd forC₂₆H₃₃Si₂ [(M+H)—H₂]: 401.2121. found 401.2120.

((3-Ethynylphenyl)ethynyl)dimethyl(phenyl)silane 6a

The general procedure was followed. The reaction was performed with NaOH(4.0 mg, 0.1 mmol, 20 mol %), 1,3-diethynylbenzene (63 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 48 h. The desired product 6a(99.2 mg, 76% yield) was obtained as a colorless oil after solventremoval at 85° C. at 45 mtorr for 30 minutes and subsequent purificationby silica gel flash chromatography (100% hexanes→3% EtOAc in hexanes).R_(f)=0.27 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.70-7.68 (m, 2H),7.64 (t, J=1.6 Hz, 1H), 7.46 (ddt, J=14.2, 7.8, 1.4 Hz, 2H), 7.41 (dd,J=4.9, 1.9 Hz, 3H), 7.29 (dd, J=7.7, 0.6 Hz, 1H), 3.09 (s, 1H), 0.51 (d,J=0.5 Hz, 6H); ¹³C NMR (126 MHz, CDCl₃) δ 136.86, 135.71, 133.86,132.38, 132.35, 129.66, 128.48, 128.09, 123.43, 122.51, 105.63, 93.20,82.78, 77.99, −0.75. IR (Neat Film NaCl) 3294, 2950, 2152, 1474, 1428,1249, 1118, 924, 838, 818, 781, 731, 698 cm⁻¹; HRMS (EI+) calc'd forC₁₈H₁₇Si [M+H]: 261.1100. found 261.1093.

1,3-bis((dimethyl(phenyl)silyl)ethynyl)benzene 6b

The general procedure was followed. The reaction was performed with NaOH(4.0 mg, 0.1 mmol, 20 mol %), 1,3-diethynylbenzene (63 mg, 0.5 mmol, 1.0equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 65° C. for 48 h. The desired product 6b(173.5 mg, 88% yield) was obtained in 95% purity after solvent removalat 85° C. at 45 mtorr for 30 minutes; subsequent purification by silicagel flash chromatography (100% hexanes→3% EtOAc in hexanes) yielded theproduct 6b in analytically pure form as a light yellow oil. R_(f)=0.26(100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ 7.73-7.70 (m, 4H), 7.69 (t,J=1.7 Hz, 1H), 7.47 (dd, J=7.8, 1.7 Hz, 2H), 7.44-7.41 (m, 6H), 7.28(ddd, J=8.0, 7.4, 0.5 Hz, 1H), 0.53 (s, 12H); ¹³C NMR (126 MHz, CDCl₃) δ136.88, 135.69, 133.86, 132.23, 129.64, 128.40, 128.08, 123.33, 105.73,93.08, −0.74. IR (Neat Film NaCl) 3068, 2959, 2153, 1589, 1474, 1428,1405, 1249, 1164, 1118, 944, 838, 816, 780, 753, 730, 702, 685 cm⁻¹;HRMS (EI+) calc'd for C₂₆H₂₇Si₂ [M+H]: 395.1651. found 395.1659.

Example 3.4 Synthesis of Symmetric and Unsymmetric Diethynylsilanes

Bis(3-cyclohexylprop-1-yn-1-yl)diethylsilane 7

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), Et₂SiH₂ (24 mg, 36 μL, 0.275 mmol, 0.55 equiv), and 0.5 mL oftetrahydrofuran (THF) at 45° C. for 48 h. The desired product 7 (125.0mg, 76% yield) was obtained in 90% purity after solvent removal underhigh vacuum at 45 mtorr for 30 minutes; subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 7 asa colorless oil. R_(f)=0.51 (100% hexanes); ¹H NMR (500 MHz, CDCl₃) δ2.15 (d, J=6.6 Hz, 4H), 1.81 (ddd, J=13.6, 4.0, 1.8 Hz, 4H), 1.72 (dt,J=12.7, 3.2 Hz, 4H), 1.65 (dddt, J=12.7, 5.1, 3.3, 1.5 Hz, 2H), 1.49(dddt, J=14.6, 8.0, 6.7, 3.2 Hz, 2H), 1.25 (qt, J=12.7, 3.4 Hz, 4H),1.15 (tt, J=12.6, 3.2 Hz, 4H), 1.05 (t, J=7.8 Hz, 6H), 1.03-0.98 (m,2H), 0.67 (q, J=7.8 Hz, 4H). ¹³C NMR (126 MHz, CDCl₃) δ 108.03, 80.73,37.36, 32.76, 27.95, 26.43, 26.29, 7.47, 7.02. IR (Neat Film NaCl) 2923,2873, 2852, 2175, 1448, 1031, 725, 688 cm⁻¹; HRMS (EI+) calc'd forC₂₂H₃₇Si [M+H]: 329.2665. found 329.2661.

(3-Cyclohexylprop-1-yn-1-yl)(cyclopropylethynyl)diethylsilane 8

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), cyclohexylpropyne (61 mg, 0.5 mmol, 1.0equiv), cyclopropylacetylene (36 mg, 0.55 mmol, 1.1 equiv), Et₂SiH₂ (49mg, 71 μL, 0.55 mmol, 1.1 equiv), and 0.5 mL of 1,2-dimethoxyethane(DME) at 45° C. for 24 h, then 65° C. for 48 h. The desired product 8(102.8 mg, 76% yield) was obtained in 90% purity after solvent removalunder high vacuum at 45 mtorr for 30 minutes; subsequent purification bysilica gel flash chromatography (100% hexanes) yielded the product 8 asa colorless oil. Also isolated was 10% yield of the homocoupled3-cyclohexyl-1-propyne product 7; <5% of the homocoupledcyclopropylacetylene 8-SI was identified by GC-MS. This same product 8can be achieved in comparable yield (106.4 mg, 78% yield) in a 2-stepprocess by first isolating the silylated cyclohexylpropyne 2e and thencombining this pre-silylated product with cyclopropylacetylene (1.1equiv) and NaOH (10 mol %). R_(f)=0.34 (100% hexanes); ¹H NMR (500 MHz,CDCl₃) δ 2.14 (d, J=6.6 Hz, 2H), 1.83-1.77 (m, 2H), 1.71 (dt, J=12.7,3.2 Hz, 2H), 1.65 (dddt, J=12.8, 5.1, 3.3, 1.5 Hz, 1H), 1.48 (ddtd,J=15.0, 11.6, 6.8, 3.6 Hz, 1H), 1.33-1.28 (m, 1H), 1.28-1.19 (m, 2H),1.13 (qt, J=12.8, 3.3 Hz, 1H), 1.03 (t, J=7.9 Hz, 6H), 1.01-0.95 (m,2H), 0.81-0.73 (m, 4H), 0.65 (q, J=7.9 Hz, 4H); ¹³C NMR (126 MHz, CDCl₃)δ 111.83, 108.11, 80.57, 75.08, 37.34, 32.76, 27.94, 26.41, 26.27, 8.98,7.43, 6.98, 0.73. IR (Neat Film NaCl) 3422, 3094, 3012, 2955, 1923,2852, 2174, 2105, 1641, 1449, 1424, 1376, 1348, 1322, 1275, 1232, 1130,1073, 1052, 1028, 979, 891, 873, 828, 779, 725, 688, 642 cm⁻¹; HRMS(EI+) calc'd for C₁₈H₂₉Si [M+H]: 273.2039. found 273.2025.

Example 3.5 Late-Stage Silylation of Pharmaceuticals

N-benzyl-3-(dimethyl(phenyl)silyl)-N-methylprop-2-yn-1-amine 9

The general procedure was followed. The reaction was performed with NaOH(2.0 mg, 0.05 mmol, 10 mol %), Pargyline(N-benzyl-N-methylprop-2-yn-1-amine) (80 mg, 0.5 mmol, 1.0 equiv),PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0 equiv), and 0.5 mL of1,2-dimethoxyethane (DME) at 45° C. for 24 h. The desired product 9(140.4 mg, 96% yield) was obtained as a pale yellow oil after solventremoval at 85° C. at 45 mtorr for 30 minutes. ¹H NMR (500 MHz, CDCl₃) δ7.69 (dq, J=6.8, 3.4, 2.7 Hz, 2H), 7.40 (dt, J=4.3, 2.1 Hz, 3H),7.35-7.31 (m, 4H), 7.30-7.26 (m, 1H), 3.60 (d, J=3.0 Hz, 2H), 3.38 (d,J=3.1 Hz, 2H), 2.38 (d, J=3.2 Hz, 3H), 0.47 (d, J=3.4 Hz, 6H); ¹³C NMR(126 MHz, CDCl₃) δ 138.47, 137.34, 133.82, 129.54, 129.39, 128.45,128.01, 127.35, 102.95, 88.41, 60.17, 46.08, 42.09, −0.49. IR (Neat FilmNaCl) 3067, 3026, 2958, 2793, 2162, 1494, 1453, 1428, 1366, 1249, 1115,1026, 980, 837, 817, 780, 732, 698 cm⁻¹; HRMS (EI+) calc'd for C₁₉H₂₄NSi[M+H]: 294.1678. found 294.1689.

(((8R,9S,13S,14S,17S)-17-((dimethyl(phenyl)silyl)ethynyl)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)oxy)dimethyl(phenyl)silane 10a

The general procedure was followed. The reaction was performed with KOH(2.8 mg, 0.05 mmol, 10 mol %), mestranol((8R,9S,13S,14S,17R)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol)(155 mg, 0.5 mmol, 1.0 equiv), PhMe₂SiH (204 mg, 230 μL, 1.5 mmol, 3.0equiv), and 0.5 mL of 1,2-dimethoxyethane (DME) at 45° C. for 24 h then65° C. for 48 h. The product 10a (185.5 mg, 64% yield) was obtained as acolorless oil by silica gel flash chromatography (1%→5% EtOAc inhexanes). R_(f)=0.50 (5% EtOAc in hexanes); ¹H NMR (500 MHz, THF-d8) δ7.62-7.56 (m, 4H), 7.30 (dtq, J=9.6, 5.1, 2.2 Hz, 6H), 7.16 (d, J=8.6Hz, 1H), 6.63 (dd, J=8.5, 2.7 Hz, 1H), 6.59-6.55 (m, 1H), 3.69 (d, J=1.0Hz, 3H), 2.88-2.75 (m, 2H), 2.42-2.23 (m, 2H), 2.18 (qd, J=10.8, 10.1,3.5 Hz, 1H), 2.11-1.95 (m, 2H), 1.94-1.85 (m, 1H), 1.83-1.74 (m, 2H),1.54-1.38 (m, 4H), 1.34 (ddt, J=24.2, 12.3, 5.9 Hz, 1H), 0.94 (d, J=2.0Hz, 3H), 0.52-0.43 (m, 6H), 0.38-0.32 (m, 6H). ¹³C NMR (126 MHz, THF-d8)δ 158.87, 140.78, 138.42, 134.65, 134.38, 133.09, 130.31, 129.98,128.73, 128.45, 127.12, 114.47, 112.88, 112.37, 90.44, 82.68, 55.34,51.46, 49.86, 45.16, 41.66, 40.95, 34.17, 30.86, 28.64, 27.69, 24.01,17.10, 13.81, 1.44, −0.61. IR (Neat Film NaCl) 3417, 3068, 3048, 2946,2869, 2234, 2160, 2081, 1610, 1575, 1500, 1465, 1427, 1279, 1252, 1136,1117, 1088, 1045, 929, 886, 818, 783, 730, 699, 642 cm⁻¹; HRMS (EI+)calc'd for C₃₇H₄₇O₂Si₂ [M+H]: 579.3115. found 579.3109.

(8R,9S,13S,14S,17S)-17-((dimethyl(phenyl)silyl)ethynyl)-3-methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol10b

The desired product 10b (40.0 mg, 18% yield) was also obtained from thisreaction as a white solid foam by silica gel flash chromatography (1%→5%EtOAc in hexanes) in a 9:1 mixture with 10a. R_(f)=0.39 (5% EtOAc inhexanes); ¹H NMR (500 MHz, THF-d8) δ 7.62-7.56 (m, 2H), 7.32-7.27 (m,3H), 7.05 (dd, J=8.8, 0.9 Hz, 1H), 6.60 (dd, J=8.5, 2.8 Hz, 1H), 6.57(d, J=2.7 Hz, 1H), 5.68 (s, 1H), 3.71 (s, 3H), 2.82-2.78 (m, 2H),2.33-2.26 (m, 1H), 2.24-2.16 (m, 3H), 2.00 (ddd, J=13.3, 11.9, 4.1 Hz,1H), 1.90-1.81 (m, 3H), 1.68-1.60 (m, 1H), 1.40-1.27 (m, 4H), 0.91 (s,3H), 0.44 (d, J=1.5 Hz, 6H); ¹³C NMR (126 MHz, THF-d8) δ 158.91, 140.86,138.41, 134.21, 132.92, 130.05, 128.59, 127.30, 114.45, 112.45, 91.04,82.87, 55.37, 49.97, 48.26, 45.20, 40.94, 40.81, 37.16, 34.18, 30.91,28.64, 27.77, 24.00, 14.21, 1.45. IR (Neat Film NaCl) 3421, 2932, 2869,1609, 1500, 1464, 1427, 1979, 1253, 1138, 1117, 1099, 1035, 888, 829,783, 742, 699 cm⁻¹; HRMS (EI+) calc'd for C₂₉H₃₇O₂Si [M+H]: 445.2563.found 445.2575.

As those skilled in the art will appreciate, numerous modifications andvariations of the present invention are possible in light of theseteachings, and all such are contemplated hereby. For example, inaddition to the embodiments described herein, the present inventioncontemplates and claims those inventions resulting from the combinationof features of the invention cited herein and those of the cited priorart references which complement the features of the present invention.Similarly, it will be appreciated that any described material, feature,or article may be used in combination with any other material, feature,or article, and such combinations are considered within the scope ofthis invention.

What is claimed:
 1. A method comprising contacting at least one organicsubstrate comprising a terminal alkynyl C—H bond, with a mixture of atleast one organosilane and an alkali metal hydroxide, under conditionssufficient to form a silylated terminal alkynyl moiety.
 2. The method ofclaim 1, wherein at least one organosilane comprises an organosilane ofFormula (I), Formula (II), or Formula (III):(R)_(4-m)Si(H)_(m)  (I)(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)R—[—SiH(R)—O—]_(n)—R  (III) where: m and p are are independently 1, 2,or 3; q is 0, 1, 2, 3, 4, 5, or 6; r is 0 or 1; n is 10 to 100; and eachR is independently halo (e.g., F, Br, Cl, I)(provided at least one R iscontains carbon), optionally substituted C₁₋₁₂ alkyl or heteroalkyl,optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, optionallysubstituted C₁₋₁₂ alkynyl or heteroalkynyl, optionally substituted C₅₋₂₀aryl or C₃₋₂₀ heteroaryl, optionally substituted C₆₋₃₀ alkaryl orheteroalkaryl, optionally substituted C₅₋₃₀ aralkyl or heteroaralkyl,optionally substituted —O—C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted —O—C₅₋₂₀ aryl or —O—C₃₋₂₀ heteroaryl, optionally substituted—O—C₅₋₃₀ alkaryl or heteroalkaryl, or optionally substituted —O—C₅₋₃₀aralkyl or heteroaralkyl, and, if substituted, the substituents may bephosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or ametal-containing or metalloid-containing group, where the metalloid isSn or Ge, where the substituents may optionally provide a tether to aninsoluble or sparingly soluble support media comprising alumina, silica,or carbon.
 3. The method of claim 2, wherein the organosilane is(R)₃SiH, (R)₂SiH₂, or (R)SiH₃, where R is independently alkoxy, alkyl,alkenyl, aryl, aryloxy, heteroaryl, aralkyl, or heteroaralkyl.
 4. Themethod of claim 1, wherein the alkali metal hydroxide is sodiumhydroxide (NaOH).
 5. The method of claim 4, wherein the organosilane isEtMe₂SiH, (n-Bu)₃SiH, Et₂SiH₂, PhMe₂SiH, BnMe₂SiH, (EtO)₃SiH,Me₂(pyridinyl)SiH, or Me₃Si—SiMe₂H
 6. The method of claim 1, wherein thealkali metal hydroxide is potassium hydroxide (KOH).
 7. The method ofclaim 6, wherein the organosilane is EtMe₂SiH, PhMe₂SiH, (n-Bu)₃SiH,Et₂SiH₂, (i-Pr)₃SiH, or (i-Pr)₂(pyridinyl)SiH.
 8. The method of claim 1,wherein the organic substrate comprising the terminal alkynyl C—H bondhas a formula:R¹—C≡C—H, where R¹ comprises H, an optionally substituted alkyl,optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl, optionally substituted heteroalkyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroaralkyl, or optionally substitutedmetallocene.
 9. The method of claim 8, wherein R¹ is or comprises: (a)an optionally substituted linear alkyl, an optionally substitutedbranched alkyl, or an optionally substituted cycloalkyl; (b) anoptionally substituted linear alkenyl, an optionally substitutedbranched alkenyl, or an optionally substituted cycloalkenyl; (c) anoptionally substituted linear heteroalkyl, an optionally substitutedbranched heteroalkyl, or an optionally substituted heterocycloalkyl; (d)an optionally substituted aryl, an optionally substituted aralkyl,optionally substituted heteroaryl, or an optionally substitutedheteroaralkyl; or (e) a combination of two or more of (a) through (d).10. The method of claim 1, wherein the organic substrate comprising theterminal alkynyl C—H bond is polymeric.
 11. The method of claim 1,wherein the at least one organosilane is (R)₂Si(H)₂, further comprisingcontacting a second organic substrate comprising a terminal alkynyl C—Hbond with the silylated terminal alkynyl moiety to form a di- ortri-alkynyl cross-coupled silane product.
 12. The method of claim 1,further comprising polymerizing the silylated terminal alkynyl moiety.13. The method of claim 1, further comprising reacting the silylatedterminal alkynyl moiety with: (a) another unsaturated moiety in a [2+2]or [4+2] cycloaddition reaction to form an aromatic, heteroaromatic,cycloalkenyl, or heterocycloalkenyl moiety; (b) a second, unsaturatedorganic moiety in a cross-metathesis reaction to form a diolefin orpolyolefin product; (c) an organic azide in a [3+2] azide-alkynecycloaddition reaction; (d) hydrogen, water, an alcohol, hydrogencyanide, hydrogen chloride, dihalogen, or carboxylic acids to givecorresponding olefin or alkane, vinyl compounds, or carbonyl compound;(e) an aromatic halide compound under conditions sufficient to form analkynyl-arene linkage; (f) an N-halosuccinimide in the presence of acationic gold catalyst to produce a terminal alkynyl halide; or (g) anycombination of (a) through (f).
 14. The method of claim 1, furthercomprising removing the silyl group originally added to the terminalalkynyl C—H bond.
 15. The method of claim 1, wherein the at least oneorganosilane comprises an optionally substituted C₁₋₁₂ alkenyl orheteroalkenyl, such that the silylated terminal alkynyl moiety comprisesa silicon bonded optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl,the method further comprising reacting the silylated terminal alkynylmoiety with an alcohol and a catalyst under conditions to result in theintramolecular allylation of the silylated terminal alkynyl moiety. 16.The method of claim 1, wherein the at least one organosilane comprises a2-pyridinyl group, the method further comprising: (a) reacting thesilylated terminal alkynyl moiety with a copper carbomagnesationcatalyst and an optionally substituted aryl or optionally substitutedheteroaryl magnesium complex under conditions sufficient tocarbomagnesate the silylated terminal alkynyl moiety; and thenoptionally (b) reacting the carbomagnesated silylated terminal alkynylmoiety with an optionally substituted aryl iodide or optionallysubstituted heteroaryl iodide in the presence of a palladium catalyst toform a trisubstituted silylated olefin; and then optionally (c) reactingthe trisubstituted silylated olefin with BCl₃ and pinacol underconditions sufficient to borodesilylate the compound, and thenoptionally (d) reacting the borodesilylated compound with a secondoptionally substituted aryl iodide or optionally substituted heteroaryliodide under conditions suitable to cross-couple the resulting C—B bondand the second optionally substituted aryl iodide or optionallysubstituted heteroaryl iodide.
 17. A system for silylating an organicsubstrate comprising a terminal alkynyl C—H bond, said system comprisingor consisting essentially of a mixture of (a) at least one organosilaneand (b) an alkali metal hydroxide or alkoxide, and (c) at least onesubstrate comprising a terminal alkynyl C—H bond.
 18. The system ofclaim 17, wherein at least one organosilane comprises an organosilane ofFormula (I), Formula (II), or Formula (III):(R)_(4-m)Si(H)_(m)  (I)(R)_(3-m)(H)_(m)Si—(CH₂)_(q)—O_(r)—Si(R)_(3-p)(H)_(p)  (II)R—[—SiH(R)—O—]_(n)—R  (III) where: m and p are are independently 1, 2,or 3; q is 0, 1, 2, 3, 4, 5, or 6; r is 0 or 1; n is 10 to 100; and eachR is independently halo (e.g., F, Br, Cl, I)(provided at least one R iscontains carbon), optionally substituted C₁₋₁₂ alkyl or heteroalkyl,optionally substituted C₁₋₁₂ alkenyl or heteroalkenyl, optionallysubstituted C₁₋₁₂ alkynyl or heteroalkynyl, optionally substituted C₅₋₂₀aryl or C₃₋₂₀ heteroaryl, optionally substituted C₆₋₃₀ alkaryl orheteroalkaryl, optionally substituted C₅₋₃₀ aralkyl or heteroaralkyl,optionally substituted —O—C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted —O—C₅₋₂₀ aryl or —O—C₃₋₂₀ heteroaryl, optionally substituted—O—C₅₋₃₀ alkaryl or heteroalkaryl, or optionally substituted —O—C₅₋₃₀aralkyl or heteroaralkyl, and, if substituted, the substituents may bephosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or ametal-containing or metalloid-containing group, where the metalloid isSn or Ge, where the substituents may optionally provide a tether to aninsoluble or sparingly soluble support media comprising alumina, silica,or carbon. In some embodiments for Formula (II), q is
 0. In someembodiments for Formula (II), r is
 0. 19. The system of claim 18,wherein the alkali metal hydroxide is sodium hydroxide (NaOH) orpotassium hydroxide.
 20. The system of claim 19, wherein theorganosilane is EtMe₂SiH, (n-Bu)₃SiH, (i-Pr)₃SiH, Et₂SiH₂, PhMe₂SiH,BnMe₂SiH, (Me)₂(pyridinyl)SiH, (i-Pr)₂(pyridinyl)SiH, (EtO)₃SiH, orMe₃Si—SiMe₂H
 21. The system of claim 17, wherein the organic substratecomprising the terminal alkynyl C—H bond has a formula:R¹—C≡C—H, where R¹ comprises H, an optionally substituted alkyl,optionally substituted alkenyl, optionally substituted alkynyl,optionally substituted aryl, optionally substituted heteroalkyl,optionally substituted heteroaryl, optionally substituted aralkyl,optionally substituted heteroaralkyl, or optionally substitutedmetallocene.
 22. The system of claim 21, wherein R¹ is or comprises: (a)an optionally substituted linear alkyl, an optionally substitutedbranched alkyl, or an optionally substituted cycloalkyl; (b) anoptionally substituted linear heteroalkyl, an optionally substitutedbranched heteroalkyl, or an optionally substituted heterocycloalkyl; (c)an optionally substituted aryl, an optionally substituted aralkyl,optionally substituted heteroaryl, or an optionally substitutedheteroaralkyl; or (d) a combination of two or more of (a) through (d).23. The system of claim 17, comprising at least two differentorganosilanes.
 24. The system of claim 17, comprising at least twodifferent organic substrates, each comprising a terminal alkynyl C—Hbond.